About BRAF
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRAF c.1068A>G, p.(Gln356=)
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.
Words with a dotted underline have a short definition. Hover or tap them.
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 BRAF VCEP v2.3.0. 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 variant has a gnomAD filtering allele frequency (grpmax FAF) of 0.1388% in v2.1 and 0.1350% in v4.1, exceeding the CSPEC RASopathy VCEP BA1 threshold of ≥0.05%. This is consistent with a benign population polymorphism for a dominant RASopathy disorder.
BS1Strong
BS1 · strong
The variant has a gnomAD filtering allele frequency (grpmax FAF) of 0.1388% in v2.1 and 0.1350% in v4.1, exceeding the CSPEC RASopathy VCEP BS1 threshold of ≥0.025%. The observed frequency in the general population is inconsistent with a highly penetrant dominant RASopathy disorder.
BS2Strong
BS2 · strong
Homozygotes for this variant are observed in gnomAD (1 in v2.1, 2 in v4.1). For a dominant disorder such as RASopathy with full penetrance expected at an early age, observation of homozygous healthy individuals in population databases constitutes strong evidence for a benign classification.
BP4Supporting
BP4 · supporting
CSPEC RASopathy VCEP BP4 for splicing variants requires predicted outcome to be negligible or not matching disease mechanism. SpliceAI predicts no significant splice impact for this synonymous variant (max delta score 0.01), satisfying the BP4 criteria for a negligible predicted splicing outcome.
BP6Supporting
BP6 · supporting
Expert panel ClinGen RASopathy Variant Curation Expert Panel classified as Benign.
BP7Supporting
BP7 · supporting
This is a synonymous (silent) variant (p.Gln356=) for which SpliceAI predicts no impact to the splice consensus sequence nor creation of a new splice site (max delta 0.01). The nucleotide is not in a known highly conserved functional element within the critical domains defined by the VCEP. BP7 is applied in conjunction with BP4 per CSPEC guidance.
Recorded classification: Benign
ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRAF Version 2.3.0 v2.3.0 criteria-combination framework: matched Rule17 (1 Benign.Stand Alone) with applied criteria: BA1 stand-alone benign, BS1 strong benign, BS2 strong benign, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; 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
225 / 1,614,110 alleles
gnomAD v4.1: 225 / 1,614,110 alleles. Recorded AF 0.000139396. Recorded homozygote count 2.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000254554; MAF= 0.02546%, 72/282848 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00176378; MAF= 0.17638%, 54/30616 alleles, homozygotes = 1); grpmax FAF= 0.00138788.
No screenshot for this evidence
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
6 Benign · 3 Likely benign.
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 ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRAF VCEP v2.3.0, with the data and sources behind each one.
26 criteria with recorded statuses: 6 met · 6 not met · 7 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The variant NM_001354609.1:c.1068A>G (p.Gln356=) is a synonymous substitution in BRAF exon 8, outside the critical functional domains defined by the ClinGen RASopathy VCEP.
This variant is present in gnomAD v2.1 at an allele frequency of 0.02546% (72/282,848 alleles, 1 homozygote) with a grpmax filtering allele frequency of 0.1388%, and in gnomAD v4.1 at 0.01394% (225/1,614,110 alleles, 2 homozygotes) with a grpmax FAF of 0.1350%.
BA1 is met at stand-alone benign strength: the gnomAD grpmax FAF of 0.1388% (v2.1) and 0.1350% (v4.1) exceeds the CSPEC RASopathy VCEP threshold of ≥0.05%.
BS1 is met at strong benign strength: the gnomAD grpmax FAF exceeds the CSPEC RASopathy VCEP threshold of ≥0.025%.
BS2 is met at strong level: homozygous individuals are observed in gnomAD (1 in v2.1, 2 in v4.1), which is inconsistent with a highly penetrant autosomal dominant RASopathy disorder.
BP4 is met at supporting benign strength: SpliceAI predicts no significant splice impact (max delta 0.01), satisfying the VCEP BP4 criterion for negligible predicted splicing outcome.
BP7 is met at supporting benign strength: the variant is synonymous (p.Gln356=) with no predicted splice impact (SpliceAI delta 0.01), applied in conjunction with BP4.
The ClinGen RASopathy Variant Curation Expert Panel has classified this variant as Benign (ClinVar Variation ID 44788), applying criteria BA1, BS1, BP4, and BP7, consistent with this independent assessment.
Under the CSPEC RASopathy VCEP v2.3.0 classification framework Rule 17, BA1 alone (stand-alone benign) is sufficient for a Benign classification. Additionally, BS1 (strong) and BS2 (strong) satisfy Rule 16 (≥2 strong benign criteria). The variant is classified as Benign.
No criteria match.
Met · 6
BA1 Stand aloneThe variant has a gnomAD filtering allele frequency (grpmax FAF) of 0.1388% in v2.1 and 0.1350% in v4.1, exceeding the CSPEC RASopathy VCEP BA1 threshold of ≥0.05%. This is consistent with a benign population polymorphism for a dominant RASopathy disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF 0.1388% ≥ 0.05% threshold
- gnomAD v4.1 grpmax FAF 0.1350% ≥ 0.05% threshold
- CSPEC BA1 rule satisfied
Sources
BS1 StrongThe variant has a gnomAD filtering allele frequency (grpmax FAF) of 0.1388% in v2.1 and 0.1350% in v4.1, exceeding the CSPEC RASopathy VCEP BS1 threshold of ≥0.025%. The observed frequency in the general population is inconsistent with a highly penetrant dominant RASopathy disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF 0.1388% ≥ 0.025% threshold
- gnomAD v4.1 grpmax FAF 0.1350% ≥ 0.025% threshold
- CSPEC BS1 rule satisfied
Sources
BS2 StrongHomozygotes for this variant are observed in gnomAD (1 in v2.1, 2 in v4.1). For a dominant disorder such as RASopathy with full penetrance expected at an early age, observation of homozygous healthy individuals in population databases constitutes strong evidence for a benign classification. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 1 homozygote (72 total alleles)
- gnomAD v4.1: 2 homozygotes (225 total alleles)
- homozygotes in presumably healthy population controls for an autosomal dominant disorder
Sources
BP4 SupportingCSPEC RASopathy VCEP BP4 for splicing variants requires predicted outcome to be negligible or not matching disease mechanism. SpliceAI predicts no significant splice impact for this synonymous variant (max delta score 0.01), satisfying the BP4 criteria for a negligible predicted splicing outcome. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01
- no predicted splicing impact
- satisfies VCEP BP4 for negligible splicing outcome
Sources
BP6 SupportingExpert panel ClinGen RASopathy Variant Curation Expert Panel classified as Benign. Details ▾Hide ▴
BP7 SupportingThis is a synonymous (silent) variant (p.Gln356=) for which SpliceAI predicts no impact to the splice consensus sequence nor creation of a new splice site (max delta 0.01). The nucleotide is not in a known highly conserved functional element within the critical domains defined by the VCEP. BP7 is applied in conjunction with BP4 per CSPEC guidance. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.Gln356=
- SpliceAI delta 0.01 (no splice impact)
- applied in conjunction with BP4 per VCEP BP7 guidance
Sources
Not met · 6 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change as a previously established pathogenic variant. This synonymous variant produces no amino acid change (p.Gln356=), so no pathogenic comparator with the same amino acid change exists. Details ▾Hide ▴
Evidence considered
- Variant is synonymous
- no amino acid change to compare against known pathogenic missense variants at this position
Sources
PS4 The variant is present in gnomAD at population frequencies (v2.1: 0.02546%, 72/282,848 alleles; v4.1: 0.01394%, 225/1,614,110 alleles) that far exceed any plausible enrichment in RASopathy cases. The ClinGen RASopathy VCEP has classified this variant as Benign, confirming no case enrichment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF 0.02546% with 1 homozygote
- gnomAD v4.1 AF 0.01394% with 2 homozygotes
- ClinVar expert panel classified as Benign
Sources
PM1 CSPEC RASopathy VCEP restricts PM1 to critical and well-established functional domains: exon 6, exon 11, P-loop (AA 459-474), and CR3 activation segment (AA 594-627). Codon 356 resides in exon 8, outside any of these specified critical domains. Details ▾Hide ▴
Evidence considered
- Codon 356 is in exon 8
- not within VCEP-defined critical domains (exon 6
- exon 11
- P-loop AA 459-474
- CR3 AA 594-627)
Sources
PM2 CSPEC RASopathy VCEP requires the variant to be absent from controls (gnomAD) for PM2_Supporting. The variant is present in gnomAD v2.1 (72 alleles, AF 0.02546%) and v4.1 (225 alleles, AF 0.01394%), failing the absence requirement. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 72/282
- 848 alleles
- gnomAD v4.1: 225/1
- 614
- 110 alleles
- variant is not absent from population controls
Sources
PP3 CSPEC RASopathy VCEP PP3 for missense variants requires REVEL ≥ 0.7. REVEL score is unavailable for this synonymous variant. For splicing impact, SpliceAI delta is 0.01, predicting no significant splice alteration, which does not match a gain-of-function disease mechanism. Details ▾Hide ▴
Evidence considered
- REVEL score unavailable (synonymous variant)
- SpliceAI max delta 0.01 predicts no splicing impact
Sources
PS5 PS5 (generic ACMG/AMP 2015) requires a reputable source to have recently reported the variant as pathogenic. ClinVar classifies this variant as Benign after expert panel review by the ClinGen RASopathy VCEP. No reputable source reports it as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Benign (expert panel)
- no source reports this variant as pathogenic
Sources
Not assessed · 7 · no assessment recorded
PS2 No confirmed de novo occurrences (with maternity and paternity confirmation) have been reported in RASopathy patients for this variant. The variant's presence in gnomAD at appreciable frequency with homozygotes makes de novo pathogenicity highly unlikely. Details ▾Hide ▴
Evidence considered
- Exploratory search found no de novo reports
- variant is present in general population (gnomAD) with homozygous individuals
Still missing
- No published de novo observations for this variant
Sources
PS3 No dedicated in vitro functional assay data (e.g., minigene splicing, kinase activity) has been identified for this exact variant. SpliceAI predicts no significant splice impact (max delta 0.01), but this in silico prediction alone does not constitute PS3-level functional evidence. Details ▾Hide ▴
Evidence considered
- SpliceAI delta 0.01 predicts no splicing impact
- no wet-lab functional studies found for this variant
Still missing
- No approved functional assay data per the VCEP SVI-RASopathy-VCEP-V2-Approved-Functional-Studies framework
Sources
PM6 No assumed de novo occurrences (without maternity/paternity confirmation) have been reported for this variant in RASopathy probands. The variant's population frequency makes de novo events unlikely. Details ▾Hide ▴
Evidence considered
- No reported assumed de novo occurrences
- variant is common in population controls
Still missing
- No published assumed de novo observations
Sources
PP1 No published multigenerational families demonstrating cosegregation of this variant with RASopathy in multiple affected relatives. Given the variant's population frequency and the VCEP's benign classification, mendelian segregation with disease is unlikely. Details ▾Hide ▴
Evidence considered
- No cosegregation data identified
- variant is common in population controls making disease segregation improbable
Still missing
- No published family studies with segregation data for this variant
Sources
BS4 No published segregation data (lack of cosegregation with disease in affected families) has been identified for this variant. The ClinGen RASopathy VCEP did not apply BS4 in their published benign assessment (citing BA1, BS1, BP4, BP7 instead). Details ▾Hide ▴
Evidence considered
- No segregation data available
- VCEP assessment did not include BS4
Still missing
- No family studies demonstrating lack of segregation with RASopathy
Sources
BP2 No evidence has been identified of this variant occurring in trans with a known pathogenic BRAF variant in a RASopathy patient. The CSPEC BP2 point-based system requires documented co-occurrence data. Details ▾Hide ▴
Evidence considered
- No co-occurrence data with pathogenic BRAF variants identified in ClinVar
- literature
- or LOVD
Still missing
- No documented observations of this variant in trans with a pathogenic BRAF variant
BP5 The CSPEC RASopathy VCEP BP5 criterion uses a point-based system. No specific evidence has been identified to support BP5 scoring for this variant. Details ▾Hide ▴
Evidence considered
- No evidence identified to support BP5 point-based scoring
Still missing
- No evidence for BP5 point system
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPCSPEC RASopathy VCEP v2.3.0 designates PVS1 as Not Applicable. The variant NM_001354609.1:c.1068A>G is synonymous (NP_001341538.1:p.(Gln356=)) and does not fall into any null-variant category (nonsense, frameshift, canonical splice). Details ▾Hide ▴
Evidence considered
- CSPEC VCEP marks PVS1 as Not Applicable
- variant is synonymous with no predicted protein truncation
Sources
PM5 N/APM5 requires a different pathogenic missense change at the same amino acid residue. This variant is synonymous (p.Gln356=) and does not alter the amino acid; there is no residue change to compare. PM5 candidates analysis confirms variant class is not missense-like. Details ▾Hide ▴
Evidence considered
- Variant is synonymous (p.=)
- no amino acid change at codon 356
- pm5_candidates confirms not_applicable for non-missense variant class
Sources
cspec ↗pm5_candidates
PP2 N/ACSPEC RASopathy VCEP PP2 rule references the missense z-score (>3.09 in gnomAD). This variant is synonymous (p.Gln356=), not a missense variant. The PP2 framework is designed for missense variants and does not apply to synonymous changes. Details ▾Hide ▴
Evidence considered
- PP2 criterion targets missense variants
- this is a synonymous variant with no amino acid substitution
Sources
PP4 VCEPCSPEC RASopathy VCEP v2.3.0 designates PP4 as Not Applicable for this gene-disease pair. Details ▾Hide ▴
PP5 VCEPCSPEC RASopathy VCEP v2.3.0 designates PP5 as Not Applicable for this gene-disease pair. Details ▾Hide ▴
BS3 VCEPCSPEC RASopathy VCEP v2.3.0 designates BS3 as Not Applicable for this gene-disease pair. Details ▾Hide ▴
BP1 N/ACSPEC RASopathy VCEP BP1 is intended for truncating (nonsense, frameshift, canonical splice site) variants in genes where the disease mechanism is gain-of-function. This variant is synonymous (p.Gln356=), not a truncating variant. Details ▾Hide ▴
Evidence considered
- Variant is synonymous
- not truncating
- BP1 applies only to truncating variants in GOF-disease genes
Sources
Identifiers
- Gene
- BRAF
- Transcript
- NM_001354609.1
- Coding (HGVS c.)
- NM_001354609.1:c.1068A>G
- Protein (HGVS p.)
- NP_001341538.1:p.(Gln356=)
- GRCh38
- chr7:140794380 T>C
- GRCh37
- chr7:140494180 T>C
- ClinVar
- 44788
Gene diagram
Every interpreted variant in BRAF, mapped onto the exon structure of NM_001354609.1. Select a row to find it on the plot.
BRAFNM_001354609.1
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 BRAF
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
225 / 1,614,110 alleles
AF 0.000139 · 2 homozygotes · FAF 0.00135
gnomAD v2.1
72 / 282,848 alleles
AF 0.000255 · 1 homozygotes · FAF 0.00139
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 0.00014 · 225 / 1,614,110 alleles · 2 hom · FAF 0.0013
| South Asian142 / 91,084 | 0.00162 hom |
| Middle Eastern7 / 6,062 | 0.0012 |
| Remaining individuals24 / 62,500 | 0.00038 |
| East Asian3 / 44,876 | 6.7e-05 |
| African/African American4 / 75,030 | 5.3e-05 |
| European (non-Finnish)42 / 1,180,008 | 3.6e-05 |
| Ashkenazi Jewish1 / 29,604 | 3.4e-05 |
| Admixed American2 / 60,010 | 3.3e-05 |
0 alternate alleles recorded in 2 other groups: European (Finnish), Amish.
gnomAD v2.1
AF 0.00025 · 72 / 282,848 alleles · 1 hom · FAF 0.0014
| South Asian54 / 30,616 | 0.00181 hom |
| East Asian3 / 19,954 | 0.00015 |
| Remaining individuals1 / 7,226 | 0.00014 |
| Ashkenazi Jewish1 / 10,370 | 9.6e-05 |
| European (non-Finnish)12 / 129,156 | 9.3e-05 |
| Admixed American1 / 35,440 | 2.8e-05 |
0 alternate alleles recorded in 2 other groups: African/African American, European (Finnish).
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000139396; MAF= 0.01394%, 225/1614110 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.001559; MAF= 0.15590%, 142/91084 alleles, homozygotes = 2); grpmax FAF= 0.00134985.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000254554; MAF= 0.02546%, 72/282848 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00176378; MAF= 0.17638%, 54/30616 alleles, homozygotes = 1); grpmax FAF= 0.00138788.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingCSPEC RASopathy VCEP BP4 for splicing variants requires predicted outcome to be negligible or not matching disease mechanism. SpliceAI predicts no significant splice impact for this synonymous variant (max delta score 0.01), satisfying the BP4 criteria for a negligible predicted splicing outcome. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta 0.01
- no predicted splicing impact
- satisfies VCEP BP4 for negligible splicing outcome
Sources
BP7 SupportingThis is a synonymous (silent) variant (p.Gln356=) for which SpliceAI predicts no impact to the splice consensus sequence nor creation of a new splice site (max delta 0.01). The nucleotide is not in a known highly conserved functional element within the critical domains defined by the VCEP. BP7 is applied in conjunction with BP4 per CSPEC guidance. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.Gln356=
- SpliceAI delta 0.01 (no splice impact)
- applied in conjunction with BP4 per VCEP BP7 guidance
Sources
PP3 CSPEC RASopathy VCEP PP3 for missense variants requires REVEL ≥ 0.7. REVEL score is unavailable for this synonymous variant. For splicing impact, SpliceAI delta is 0.01, predicting no significant splice alteration, which does not match a gain-of-function disease mechanism. Details ▾Hide ▴
Evidence considered
- REVEL score unavailable (synonymous variant)
- SpliceAI max delta 0.01 predicts no splicing impact
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
4 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
-
PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.Duzkale H et al. · 2013No paper-specific finding is recorded.
-
PMID 25741868 ↗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 S et al. · 2015No paper-specific finding is recorded.
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PMID 20301557 ↗Noonan Syndrome with Multiple Lentigines.Adam MP et al. · 1993No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
225 / 1,614,110 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
ClinVar
6 Benign · 3 Likely benign
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
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/643243119
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/44788/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-140494180-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-140794380-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001354609.1%3Ac.1…
- OncoKB ↗www.oncokb.org/gene/BRAF/Q356=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRAF+c.1068A%3EG
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000139396; MAF= 0.01394%, 225/1614110 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.001559; MAF= 0.15590%, 142/91084 alleles, homozygotes = 2); grpmax FAF= 0.00134985.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000254554; MAF= 0.02546%, 72/282848 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.00176378; MAF= 0.17638%, 54/30616 alleles, homozygotes = 1); grpmax FAF= 0.00138788.
ClinVar
This variant has been reported in ClinVar as Benign (6 clinical laboratories) and as Likely benign (3 clinical laboratories) and as Benign by ClinGen RASopathy Variant Curation Expert Panel (expert panel). (ClinVarID = 44788)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.