NF1c.846G>ABenign

Print report

Variant interpretation report

NF1 c.846G>A, p.(Gln282=)

NM_000267.3:c.846G>A NP_000258.1:p.(Gln282=) View identifiers

Classification

Benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.

Benign.A benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About NF1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 2 strong (benign) · 3 supporting (benign)
Expert rules: ClinGen NF1 VCEP v1.0.0
Other laboratories (ClinVar): 14 Benign · 9 Likely benign
Pipeline record: 20 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): The allele frequency in the South Asian subpopulation is 3.24% (gnomAD v2.1) and 3.27% (gnomAD v4.1) with 27 and 85 homozygotes respectively. The gnomAD grpmax filtering allele frequency is 3.07% (v2.1) and 3.17% (v4.1). These frequencies far exceed the 1% threshold for BA1, establishing this variant as a common population polymorphism incompatible with NF1 pathogenicity.
BS1 (strong): The overall allele frequency is 0.496% (gnomAD v2.1, 1400/282340 alleles) and 0.366% (gnomAD v4.1, 5902/1613864 alleles). This exceeds the 0.3% threshold for BS1, indicating the variant is more common than expected for a pathogenic NF1 variant.
BS2 (strong): The variant has been observed in the homozygous state in 29 individuals in gnomAD v2.1 and 90 individuals in gnomAD v4.1. Homozygosity for a variant in NF1, a gene associated with a highly penetrant autosomal dominant disorder, is incompatible with a pathogenic role.
BP4 (supporting): Multiple lines of computational evidence suggest no impact on the gene product. SpliceAI predicts no significant splicing impact (max delta 0.06). The variant is synonymous (p.Q282=) with no amino acid change and no predicted effect on splicing. No in silico tools predict a deleterious effect.
BP6 (supporting): A reputable source classifies this variant as benign. ClinVar reports 14 clinical laboratories classifying this variant as Benign and 9 as Likely benign (ClinVar variation ID 184123). The consensus across multiple independent clinical laboratories supports a benign interpretation.
BP7 (supporting): This is a synonymous variant (p.Q282=) at a nucleotide position with no predicted impact on splicing (SpliceAI max delta 0.06). The variant does not alter the primary amino acid sequence and has no predicted effect on mRNA splicing, consistent with BP7 criteria for a benign synonymous variant.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen NF1 VCEP v1.0.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 6

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 6

BA1Stand alone

BA1 · stand alone

The allele frequency in the South Asian subpopulation is 3.24% (gnomAD v2.1) and 3.27% (gnomAD v4.1) with 27 and 85 homozygotes respectively. The gnomAD grpmax filtering allele frequency is 3.07% (v2.1) and 3.17% (v4.1). These frequencies far exceed the 1% threshold for BA1, establishing this variant as a common population polymorphism incompatible with NF1 pathogenicity.

BS1Strong

BS1 · strong

The overall allele frequency is 0.496% (gnomAD v2.1, 1400/282340 alleles) and 0.366% (gnomAD v4.1, 5902/1613864 alleles). This exceeds the 0.3% threshold for BS1, indicating the variant is more common than expected for a pathogenic NF1 variant.

BS2Strong

BS2 · strong

The variant has been observed in the homozygous state in 29 individuals in gnomAD v2.1 and 90 individuals in gnomAD v4.1. Homozygosity for a variant in NF1, a gene associated with a highly penetrant autosomal dominant disorder, is incompatible with a pathogenic role.

BP4Supporting

BP4 · supporting

Multiple lines of computational evidence suggest no impact on the gene product. SpliceAI predicts no significant splicing impact (max delta 0.06). The variant is synonymous (p.Q282=) with no amino acid change and no predicted effect on splicing. No in silico tools predict a deleterious effect.

BP6Supporting

BP6 · supporting

A reputable source classifies this variant as benign. ClinVar reports 14 clinical laboratories classifying this variant as Benign and 9 as Likely benign (ClinVar variation ID 184123). The consensus across multiple independent clinical laboratories supports a benign interpretation.

BP7Supporting

BP7 · supporting

This is a synonymous variant (p.Q282=) at a nucleotide position with no predicted impact on splicing (SpliceAI max delta 0.06). The variant does not alter the primary amino acid sequence and has no predicted effect on mRNA splicing, consistent with BP7 criteria for a benign synonymous variant.

Recorded classification: Benign

Neurofibromatosis and Schwannomatosis Specification v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BS2 strong benign, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 1 stand-alone benign + 2 strong benign + 3 supporting benign, which maps to Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

5,902 / 1,613,864 alleles

gnomAD v4.1: 5,902 / 1,613,864 alleles. Recorded AF 0.00365706. Recorded homozygote count 90.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00495856; MAF= 0.49586%, 1400/282340 alleles, homozygotes = 29) and has highest observed frequency in the South Asian population (AF= 0.0324229; MAF= 3.24229%, 990/30534 alleles, homozygotes = 27); grpmax FAF= 0.0307466.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.006462474204409688, 119/18414 alleles, homozygotes = 0).

Applied · BA1, BS1, BS2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.060 maximum delta

Recorded SpliceAI maximum delta score: 0.060. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

23 reported laboratory submissions

14 Benign · 9 Likely benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

4 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV62201020, n = 4 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen NF1 VCEP v1.0.0, with the data and sources behind each one.

26 criteria with recorded statuses: 6 met · 5 not met · 5 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

BA1 is met: allele frequency of 3.24% in the South Asian subpopulation (gnomAD v2.1) with 27 homozygotes and grpmax FAF of 3.07% far exceeds the 1% stand-alone benign threshold, establishing NM_000267.3:c.846G>A as a common population polymorphism incompatible with NF1 pathogenicity.

BS1 is met: overall gnomAD allele frequency of 0.496% (v2.1, 1400/282340 alleles) exceeds the 0.3% strong benign threshold.

BS2 is met: the variant is observed in 29 homozygous individuals in gnomAD v2.1 and 90 homozygous individuals in gnomAD v4.1, which is incompatible with a highly penetrant autosomal dominant disorder like NF1.

This variant has been reported in ClinVar as Benign by 14 clinical laboratories and as Likely benign by 9 clinical laboratories, supporting BP6.

SpliceAI predicts no significant splicing impact (max delta 0.06) and the variant is synonymous (p.Q282=) with no amino acid change, supporting BP4 and BP7.

Met · 6

BA1 Stand aloneThe allele frequency in the South Asian subpopulation is 3.24% (gnomAD v2.1) and 3.27% (gnomAD v4.1) with 27 and 85 homozygotes respectively. The gnomAD grpmax filtering allele frequency is 3.07% (v2.1) and 3.17% (v4.1). These frequencies far exceed the 1% threshold for BA1, establishing this variant as a common population polymorphism incompatible with NF1 pathogenicity. Details ▾Hide ▴

Evidence considered

South Asian AF 3.24% with 27 homozygotes (v2.1)
South Asian AF 3.27% with 85 homozygotes (v4.1)
grpmax FAF 3.07% (v2.1)

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 StrongThe overall allele frequency is 0.496% (gnomAD v2.1, 1400/282340 alleles) and 0.366% (gnomAD v4.1, 5902/1613864 alleles). This exceeds the 0.3% threshold for BS1, indicating the variant is more common than expected for a pathogenic NF1 variant. Details ▾Hide ▴

Evidence considered

Overall AF 0.496% (v2.1) and 0.366% (v4.1)
both exceeding the 0.3% BS1 threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 StrongThe variant has been observed in the homozygous state in 29 individuals in gnomAD v2.1 and 90 individuals in gnomAD v4.1. Homozygosity for a variant in NF1, a gene associated with a highly penetrant autosomal dominant disorder, is incompatible with a pathogenic role. Details ▾Hide ▴

Evidence considered

29 homozygotes in gnomAD v2.1
90 homozygotes in gnomAD v4.1

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. SpliceAI predicts no significant splicing impact (max delta 0.06). The variant is synonymous (p.Q282=) with no amino acid change and no predicted effect on splicing. No in silico tools predict a deleterious effect. Details ▾Hide ▴

Evidence considered

SpliceAI max delta 0.06 (no splicing impact)
synonymous variant with no amino acid change

Sources

spliceai ↗

BP6 SupportingA reputable source classifies this variant as benign. ClinVar reports 14 clinical laboratories classifying this variant as Benign and 9 as Likely benign (ClinVar variation ID 184123). The consensus across multiple independent clinical laboratories supports a benign interpretation. Details ▾Hide ▴

Evidence considered

ClinVar: Benign (14 clinical labs)
Likely benign (9 clinical labs)

Sources

clinvar ↗

BP7 SupportingThis is a synonymous variant (p.Q282=) at a nucleotide position with no predicted impact on splicing (SpliceAI max delta 0.06). The variant does not alter the primary amino acid sequence and has no predicted effect on mRNA splicing, consistent with BP7 criteria for a benign synonymous variant. Details ▾Hide ▴

Evidence considered

Synonymous variant p.Q282=
SpliceAI max delta 0.06 indicating no splicing impact

Sources

spliceai ↗

Not met · 5 · evaluated, threshold not reached

PS4 PS4 requires enrichment in affected individuals versus controls. This variant has a gnomAD overall allele frequency of 0.496% (v2.1) and 0.366% (v4.1) with 29 and 90 homozygotes respectively, which is incompatible with a pathogenic role in a highly penetrant autosomal dominant disorder like NF1. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF 0.496% (1400/282340 alleles
29 homozygotes)
gnomAD v4.1 AF 0.366% (5902/1613864 alleles
90 homozygotes)

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM2 PM2 requires absence or very low frequency (<0.1%) in population databases. This variant is present in gnomAD v2.1 at 0.496% (1400/282340 alleles) and v4.1 at 0.366% (5902/1613864 alleles), far exceeding the 0.1% threshold. PM2 is not met. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF 0.496%
gnomAD v4.1 AF 0.366%
both exceed PM2 threshold of <0.1%

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 PP3 requires multiple lines of computational evidence supporting a deleterious effect. SpliceAI predicts no significant splicing impact (max delta 0.06). REVEL and BayesDel scores are not available (not applicable to synonymous variants). No in silico evidence supports a deleterious effect. Details ▾Hide ▴

Evidence considered

SpliceAI max delta 0.06 (no splicing impact)
no REVEL/BayesDel applicable

Sources

spliceai ↗

PP5 PP5 requires a reputable source to have recently reported the variant as pathogenic. All ClinVar submissions classify this variant as Benign (14 labs) or Likely benign (9 labs). The ClinGen NF1 CSPEC exists (v1.0.0) but provides no variant-specific classification. No reputable source classifies this variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar classification: Benign/Likely benign
CSPEC NF1 v1.0.0 provides no variant classification

Sources

clinvar ↗cspec ↗

PS5 PS5 requires a reputable source to have reported the variant as pathogenic. All ClinVar submissions classify this variant as Benign (14 clinical laboratories) or Likely benign (9 clinical laboratories). No laboratory or reputable source has reported it as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar: Benign (14 labs)
Likely benign (9 labs)
no submissions as Pathogenic or Likely pathogenic

Sources

clinvar ↗

Not assessed · 5 · no assessment recorded

PS2 No de novo observation data available for this variant in any reviewed source. Without a specific de novo report, PS2 cannot be assessed. Details ▾Hide ▴

Still missing

No de novo reports identified

PS3 No functional studies were identified for this variant in any reviewed publication or database. Variant-specific functional evidence is absent. Details ▾Hide ▴

Still missing

No functional studies available for this variant

PP1 No segregation data are available for this variant in any reviewed publication or database. PP1 cannot be assessed without family-level cosegregation evidence. Details ▾Hide ▴

Still missing

No cosegregation data available

BS3 No functional studies have been identified for this variant in any reviewed publication or database. BS3 cannot be assessed without variant-specific functional evidence demonstrating no damaging effect. Details ▾Hide ▴

Still missing

No functional studies identified

BS4 BS4 requires documented lack of cosegregation with disease in affected family members. While the high population frequency and homozygosity strongly suggest lack of segregation with NF1, formal family-based segregation studies are not available for this variant. Details ▾Hide ▴

Still missing

No formal cosegregation studies available

Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/APVS1 is reserved for null variants (nonsense, frameshift, canonical splice sites, initiation codon, exon deletions). NM_000267.3:c.846G>A is a synonymous variant (p.Q282=) with no predicted effect on splicing (SpliceAI max delta 0.06). It does not fall into any PVS1 null-variant bucket. Details ▾Hide ▴

Evidence considered

Synonymous variant
no amino acid change
SpliceAI max delta 0.06

Sources

pvs1_variant_assessmentspliceai ↗

PS1 N/APS1 requires a different nucleotide change at the same position resulting in the same amino acid change that has been previously established as pathogenic. This is a synonymous variant with no amino acid change; PS1 is not applicable. Details ▾Hide ▴

Evidence considered

Synonymous variant (p.Q282=)
no amino acid change

PM1 N/APM1 applies to missense variants located in a mutational hotspot or critical functional domain without benign variation. This is a synonymous variant with no amino acid change; PM1 is not applicable. Additionally, the variant is not located in a statistically significant hotspot. Details ▾Hide ▴

Evidence considered

Synonymous variant
not in a statistically significant hotspot

PM5 N/APM5 requires a different pathogenic amino acid change at the same residue. This is a synonymous variant with no amino acid change. Protein consequence is p.Q282= (no change). The PM5 candidate harvest was unable to confirm classic same-residue semantics. Details ▾Hide ▴

Evidence considered

Synonymous variant (p.Q282=)
no amino acid change at this residue

Sources

pm5_candidates

PM6 N/APM6 requires a de novo observation without confirmation of paternity and maternity. No de novo data are available for this variant in any reviewed source. This criterion is not applicable. Details ▾Hide ▴

Evidence considered

No de novo observations available

PP2 N/APP2 applies to missense variants in genes where missense variants are a common disease mechanism and the gene has a low rate of benign missense variation. This is a synonymous variant, not a missense variant. Not applicable. Details ▾Hide ▴

Evidence considered

Synonymous variant
PP2 is specific to missense variants

PP4 N/APP4 requires the variant to be identified in an individual with a phenotype highly specific for the disease. No individual phenotype data are available for this variant. Not applicable without case-level clinical information. Details ▾Hide ▴

Still missing

No individual phenotype data available

BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary known disease mechanism. This is a synonymous variant with no amino acid change; BP1 is not applicable. Details ▾Hide ▴

Evidence considered

Synonymous variant
BP1 is specific to missense variants

BP2 N/ABP2 applies to a variant observed in trans with a pathogenic variant in a fully penetrant dominant disorder. Given the variant's high population frequency (0.5%), the probability of coincidental co-occurrence with a pathogenic NF1 variant is substantial; BP2 is not applicable. Details ▾Hide ▴

Evidence considered

High population frequency makes in trans observation with pathogenic variant a chance event

BP5 N/ABP5 requires the variant to be found in a case with an alternate molecular basis for disease. No case-specific data are available for this variant. Not applicable. Details ▾Hide ▴

Still missing

No case-specific data with alternate molecular basis

Identifiers

Gene: NF1
Transcript: NM_000267.3
Coding (HGVS c.): NM_000267.3:c.846G>A
Protein (HGVS p.): NP_000258.1:p.(Gln282=)
GRCh38: chr17:31182623 G>A
GRCh37: chr17:29509641 G>A
ClinVar: 184123
COSMIC: COSV62201020

Gene diagram

Every interpreted variant in NF1, mapped onto the exon structure of NM_000267.3. Select a row to find it on the plot.

NF1NM_000267.3

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in NF1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 5,902 / 1,613,864 alleles AF 0.00366 · 90 homozygotes · FAF 0.0317

gnomAD v2.1 1,400 / 282,340 alleles AF 0.00496 · 29 homozygotes · FAF 0.0307

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.0037 · 5902 / 1,613,864 alleles · 90 hom · FAF 0.032

South Asian2972 / 91,024	0.03385 hom
Middle Eastern94 / 6,060	0.016
Ashkenazi Jewish261 / 29,596	0.0088
Remaining individuals284 / 62,498	0.00451 hom
European (non-Finnish)2185 / 1,179,894	0.00194 hom
Admixed American59 / 59,998	0.00098
African/African American27 / 75,030	0.00036
European (Finnish)17 / 63,992	0.00027
East Asian3 / 44,860	6.7e-05

0 alternate alleles recorded in 1 other group: Amish.

gnomAD v2.1

AF 0.005 · 1400 / 282,340 alleles · 29 hom · FAF 0.031

South Asian990 / 30,534	0.03227 hom
Ashkenazi Jewish91 / 10,362	0.0088
Remaining individuals29 / 7,208	0.0041 hom
European (non-Finnish)243 / 128,874	0.00191 hom
Admixed American27 / 35,382	0.00076
African/African American11 / 24,948	0.00044
European (Finnish)7 / 25,092	0.00028
East Asian2 / 19,940	0.0001

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00365706; MAF= 0.36571%, 5902/1613864 alleles, homozygotes = 90) and has highest observed frequency in the South Asian population (AF= 0.0326507; MAF= 3.26507%, 2972/91024 alleles, homozygotes = 85); grpmax FAF= 0.0316716.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.006462474204409688, 119/18414 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -10 bp

0.060

SpliceAI acceptor gainat -106 bp

0.000

SpliceAI donor lossat -338 bp

0.000

SpliceAI donor gainat +102 bp

0.000

Pangolin splice lossmagnitude shown

-0.030

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta 0.06 (no splicing impact)
synonymous variant with no amino acid change

Sources

spliceai ↗

Evidence considered

Synonymous variant p.Q282=
SpliceAI max delta 0.06 indicating no splicing impact

Sources

spliceai ↗

Evidence considered

SpliceAI max delta 0.06 (no splicing impact)
no REVEL/BayesDel applicable

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).

11 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects.

Messiaen LM et al. · 2000

Messiaen et al. report exhaustive mutation analysis of NF1 identifying 95% of mutations and a high frequency of unusual splicing defects. The variant NM_000267.3:c.846G>A was not identified as a reported mutation in this paper.
Does not name this variant
PMID 10862084 ↗
NF1 gene analysis based on DHPLC.

De Luca A et al. · 2003

De Luca et al. describe DHPLC-based analysis of the NF1 gene for mutation detection. The variant NM_000267.3:c.846G>A was not identified as a reported mutation.
Does not name this variant
PMID 12552569 ↗
Molecular diagnosis of neurofibromatosis type 1: 2 years experience.

Griffiths S et al. · 2007

Griffiths et al. report two years of experience with NF1 molecular diagnostic testing through the UK Genetic Testing Network. The variant NM_000267.3:c.846G>A was not identified as a reported mutation.
Does not name this variant
PMID 16944272 ↗
A systematic approach to assessing the clinical significance of genetic variants.

Duzkale et al. describe a systematic framework for clinical variant classification developed at the Laboratory for Molecular Medicine. The paper presents general variant interpretation methodology and does not discuss any specific NF1 variant.
Does not name this variant
PMID 24033266 ↗
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards et al. present the ACMG/AMP standards and guidelines for the interpretation of sequence variants. This foundational guideline paper does not discuss any specific NF1 variant or provide variant-level evidence.
Does not name this variant
PMID 25741868 ↗
Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11-17 distinct from the GAP related domain.

Mattocks C et al. · 2004

Mattocks et al. report automated comparative sequence analysis for NF1 mutation detection, identifying mutations in 89% of NF1 patients and describing a mutation cluster in exons 11-17. The variant NM_000267.3:c.846G>A was not identified as a reported mutation in this paper.
Does not name this variant
PMID 15060124 ↗
Pitfalls of automated comparative sequence analysis as a single platform for routine clinical testing for NF1.

Messiaen LM et al. · 2005

Messiaen and Wimmer discuss pitfalls of automated comparative sequence analysis for routine NF1 clinical testing. The variant NM_000267.3:c.846G>A was not identified as a reported mutation.
Does not name this variant
PMID 15863657 ↗
Novel mutations in the NF1 gene in Czech patients with neurofibromatosis type 1.

Bendova S et al. · 2007

Bendova et al. report novel NF1 mutations identified in Czech patients with neurofibromatosis type 1. The variant NM_000267.3:c.846G>A was not identified among the reported mutations.
Does not name this variant
PMID 17726231 ↗
Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.

Lenders et al. present an Endocrine Society clinical practice guideline for pheochromocytoma and paraganglioma. This is a general clinical guideline that does not discuss specific NF1 variants.
Does not name this variant
PMID 24893135 ↗
Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.

Botkin et al. present points to consider regarding ethical, legal, and psychosocial implications of genetic testing in children and adolescents. This policy statement does not discuss specific NF1 variants.
Does not name this variant
PMID 26140447 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp et al. describe the Sherloc refinement of the ACMG-AMP variant classification criteria. This methodology paper does not discuss specific NF1 variants.
Does not name this variant
PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 5,902 / 1,613,864 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.060 Open source ↗

ClinVar 14 Benign · 9 Likely benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.006462474204409688, 119/18414 alleles, homozygotes = 0).

ClinVar

This variant has been reported in ClinVar as Benign (14 clinical laboratories) and as Likely benign (9 clinical laboratories). (ClinVarID = 184123)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV62201020, n = 4 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.