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BRCA1c.4327C>GBenign
Print report
Variant interpretation report

BRCA1 c.4327C>G, p.(Arg1443Gly)

NM_007294.4:c.4327C>G NP_009225.1:p.(Arg1443Gly) 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 BRCA1

No gene-level summary was recorded for this case.

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 BRCA1 VCEP v1.2.0. 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: 4
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 4
BS1Supporting
BS1 · supporting

The population frequency exceeds the BRCA1 BS1 supporting threshold of greater than 0.00002 but does not exceed the strong threshold of greater than 0.0001. The grpmax FAF is 2.294e-05 in gnomAD v2.1 and 3.666e-05 in gnomAD v4.1, supporting BS1 at supporting strength.

BS3Strong
BS3 · strong

In two calibrated functional studies curated by ENIGMA, this variant showed protein function similar to benign control variants and no functional impact, supporting BS3 at strong strength.

BP1Strong
BP1 · strong

This missense variant lies outside the BRCA1 clinically important functional domains defined by ENIGMA, and no splice effect is predicted. Arg1443 is outside the RING domain (aa 2-101), the coiled-coil domain (aa 1391-1424), and the BRCT repeats (aa 1650-1857), and SpliceAI shows a max delta score of 0.01, supporting BP1 at strong strength. REVEL is also low at 0.007.

BP6Supporting
BP6 · supporting

Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Benign.

Recorded classification: Benign

ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework: BS3_Strong and BP1_Strong satisfy the Benign rule requiring at least two strong benign criteria; BS1_Supporting and BP6_Supporting_Benign provide additional benign support.

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
65 / 1,613,954 alleles

gnomAD v4.1: 65 / 1,613,954 alleles. Recorded AF 4.02738e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.18291e-05; MAF= 0.00318%, 9/282760 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138581; MAF= 0.01386%, 1/7216 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.

Applied · BS1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗
No screenshot for this evidence
Computational predictions
Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

No listed criterion applied
Functional evidence
Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

Applied · BS3 → OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed

No COSMIC evidence statement is recorded in this case.

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 BRCA1 VCEP v1.2.0, with the data and sources behind each one.

28 criteria with recorded statuses: 4 met · 5 not met · 9 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The BRCA1 c.4327C>G (p.Arg1443Gly; p.R1443G) variant has been reported in ClinVar, where the aggregate classification is Benign with expert panel review.

This variant is present in population databases, including gnomAD v2.1 at 9/282760 alleles (AF 3.18291e-05; grpmax FAF 2.294e-05) and gnomAD v4.1 at 65/1613954 alleles (AF 4.02738e-05; grpmax FAF 3.666e-05), which exceeds the BRCA1 BS1 supporting threshold of 0.00002 but remains below the BA1 threshold of 0.001.

In two calibrated functional studies curated by ENIGMA, this variant showed no functional impact and protein behavior similar to benign control variants, supporting BS3 at strong strength.

Computational evidence does not support a damaging effect: SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, BayesDel no-AF is -0.285466, and REVEL is 0.007; because Arg1443 lies outside the BRCA1 ENIGMA clinically important functional domains, this profile supports BP1_Strong rather than PP3.

Met · 4

BS1 SupportingThe population frequency exceeds the BRCA1 BS1 supporting threshold of greater than 0.00002 but does not exceed the strong threshold of greater than 0.0001. The grpmax FAF is 2.294e-05 in gnomAD v2.1 and 3.666e-05 in gnomAD v4.1, supporting BS1 at supporting strength. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS1 Supporting rule
Evidence considered
  • gnomAD v2.1 grpmax FAF 2.294e-05
  • gnomAD v4.1 grpmax FAF 3.666e-05
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS3 StrongIn two calibrated functional studies curated by ENIGMA, this variant showed protein function similar to benign control variants and no functional impact, supporting BS3 at strong strength. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS3 Strong rule
Evidence considered
  • ENIGMA Table 9: BS3 Strong for c.4327C>G p.(Arg1443Gly)
  • Supplementary Table 4: no functional impact
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18PMID:30765603 ↗PMID:32546644 ↗
BP1 StrongThis missense variant lies outside the BRCA1 clinically important functional domains defined by ENIGMA, and no splice effect is predicted. Arg1443 is outside the RING domain (aa 2-101), the coiled-coil domain (aa 1391-1424), and the BRCT repeats (aa 1650-1857), and SpliceAI shows a max delta score of 0.01, supporting BP1 at strong strength. REVEL is also low at 0.007. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP1_Strong rule
Evidence considered
  • Residue 1443 is outside ENIGMA BRCA1 functional domains
  • SpliceAI max delta score 0.01
  • REVEL 0.007
Sources
cspec ↗vcep_appendices_v1_2_2024_11_18spliceai ↗revel
BP6 SupportingExpert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Benign. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
  • ClinVar expert panel classification
Sources
cspec ↗clinvar ↗

Not met · 5 · evaluated, threshold not reached

PS3 Available functional evidence does not support a damaging effect. In the ENIGMA BRCA1 functional dataset, this variant showed no functional impact and was curated as meeting BS3 rather than PS3. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS3 rule
Evidence considered
  • ENIGMA Table 9 lists c.4327C>G p.(Arg1443Gly) as BS3 Strong
  • Supplementary Table 4 records no functional impact
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18PMID:30765603 ↗PMID:32546644 ↗
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at 9/282760 alleles (AF 3.18291e-05) and in gnomAD v4.1 at 65/1613954 alleles (AF 4.02738e-05), so the BRCA1 PM2 absence-from-controls rule is not met. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM2_Supporting rule
Evidence considered
  • Observed in gnomAD v2.1
  • Observed in gnomAD v4.1
  • BRCA1 VCEP PM2 requires absence from controls
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
PP3 Computational evidence does not support a damaging effect. BayesDel no-AF is -0.285466, below the BRCA1 PP3 threshold of 0.28, and SpliceAI predicts no significant splice impact with a max delta score of 0.01, below the PP3 splice threshold of 0.2. REVEL is also low at 0.007. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP3 rule
Evidence considered
  • BayesDel no-AF -0.285466
  • SpliceAI max delta score 0.01
  • REVEL 0.007
Sources
cspec ↗spliceai ↗bayesdelrevel
BA1 The filter allele frequency does not reach the BRCA1 BA1 threshold of greater than 0.001. The observed grpmax FAF is 2.294e-05 in gnomAD v2.1 and 3.666e-05 in gnomAD v4.1, both well below that threshold. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BA1 rule
Evidence considered
  • gnomAD v2.1 grpmax FAF 2.294e-05
  • gnomAD v4.1 grpmax FAF 3.666e-05
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BP4 Available computational evidence is benign-leaning, but the BRCA1 BP4 rule is restricted to missense variants inside a clinically important functional domain with BayesDel no-AF 0.15 or lower and SpliceAI 0.1 or lower. This variant is outside those domains, so BP4 is not applied here. BayesDel is -0.285466, SpliceAI max delta score is 0.01, and REVEL is 0.007; this benign computational profile is captured by BP1_Strong rather than BP4. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP4 rule
Evidence considered
  • Variant is outside ENIGMA BRCA1 functional domains
  • BayesDel no-AF -0.285466
  • SpliceAI max delta score 0.01
  • REVEL 0.007
Sources
cspec ↗vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel

Not assessed · 9 · no assessment recorded

PS1 No reviewed evidence established a previously classified pathogenic or likely pathogenic variant with the same amino acid change or the same proven splice effect, so PS1 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS1 rule
Evidence considered
  • BRCA1 VCEP PS1 requires a previously classified pathogenic or likely pathogenic reference variant acting through the same protein or splice effect
Still missing
  • A targeted same-amino-acid/same-splice comparison source was not identified in the reviewed materials.
Sources
cspec ↗clinvar ↗
PS4 No case-control study or other reviewed dataset showed a significant enrichment of this variant in affected individuals compared with controls, so PS4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS4 rule
Evidence considered
  • BRCA1 VCEP requires significant enrichment in affected individuals versus controls
Still missing
  • No odds ratio and confidence interval meeting the BRCA1 VCEP PS4 threshold were identified.
Sources
cspec ↗clinvar ↗
PM3 No reviewed evidence showed this variant in a patient with BRCA1-related Fanconi anemia and an informative co-occurring BRCA1 variant, so PM3 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM3 rule
Evidence considered
  • BRCA1 VCEP PM3 is restricted to BRCA1/2-related Fanconi anemia context
Still missing
  • No biallelic Fanconi anemia case data were identified.
Sources
cspec ↗
PP1 No segregation analysis with a quantitative likelihood ratio was identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP1 rule
Evidence considered
  • BRCA1 VCEP PP1 requires quantitative co-segregation evidence
Still missing
  • No informative family segregation data were identified.
Sources
cspec ↗clinvar ↗
PP4 No variant-specific clinical-history likelihood ratio meeting the BRCA1 ENIGMA PP4 thresholds was identified in the reviewed materials, so PP4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP4 rule
Evidence considered
  • BRCA1 VCEP PP4 requires a calibrated multifactorial clinical likelihood ratio
Still missing
  • No exact variant match was identified in the reviewed BRCA1 clinical-history likelihood-ratio table.
Sources
cspec ↗vcep_pmid_31853058_brca1_clinical_history_lrvcep_pmid_31853058_li_2020_geneticsinmedicinePMID:31853058 ↗
BS2 No reviewed proband data were available to assign BS2 points based on absence of Fanconi anemia features, so BS2 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS2 rule
Evidence considered
  • BRCA1 VCEP BS2 requires proband-based point assignment
Still missing
  • No phenotype-level proband data for BS2 point assignment were identified.
Sources
cspec ↗
BS4 No quantitative non-segregation study or other reviewed pedigree evidence arguing against disease segregation was identified, so BS4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS4 rule
Evidence considered
  • BRCA1 VCEP BS4 requires quantitative non-segregation evidence
Still missing
  • No informative family non-segregation data were identified.
Sources
cspec ↗vcep_humu_40_1557_s001vcep_pmid_17924331_easton_2007_ajhgPMID:17924331 ↗
BP5 No variant-specific clinical-history likelihood ratio meeting the BRCA1 ENIGMA BP5 thresholds was identified in the reviewed clinical-history materials, so BP5 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP5 rule
Evidence considered
  • BRCA1 VCEP BP5 requires a calibrated multifactorial clinical likelihood ratio
Still missing
  • No exact variant match was identified in the reviewed BRCA1 clinical-history likelihood-ratio table.
Sources
cspec ↗vcep_pmid_31853058_brca1_clinical_history_lrvcep_pmid_31853058_li_2020_geneticsinmedicinePMID:31853058 ↗
BP7 No reviewed RNA study showed a normal transcript profile for this variant, so BP7 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP7 rule
Evidence considered
  • BRCA1 VCEP BP7 requires transcript-level evidence or qualifying silent/intronic context
Still missing
  • No variant-specific mRNA assay result was identified.
Sources
cspec ↗spliceai ↗
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis missense substitution does not fall into the BRCA1 PVS1 null-variant categories, and SpliceAI predicts no significant splice effect (max delta score 0.01), so PVS1 is not applicable on the reviewed evidence. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PVS1 null-variant/RNA rule
Evidence considered
  • BRCA1 VCEP PVS1 rule is limited to null variants or qualifying RNA evidence
  • Variant-level PVS1 scaffold classified this change outside default PVS1 buckets
  • SpliceAI max delta score 0.01
Sources
cspec ↗pvs1_gene_contextpvs1_variant_assessmentspliceai ↗
PS2 N/APS2 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
PM1 N/APM1 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
PM4 N/APM4 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
PM5 N/AIn the BRCA1 ENIGMA specification, PM5 is used for protein-truncating variants in eligible exons rather than for this missense substitution, so PM5 is not applicable. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM5_PTC rule
Evidence considered
  • BRCA1 VCEP PM5 rule is PTC-specific
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 N/APM6 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
PP2 N/APP2 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
PP5 N/APP5 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
BP2 N/ABP2 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗
BP3 N/ABP3 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in BRCA1 ENIGMA v1.2
Evidence considered
  • Criterion marked not applicable by BRCA1 VCEP
Sources
cspec ↗

Identifiers

Gene
BRCA1
Transcript
NM_007294.4
Coding (HGVS c.)
NM_007294.4:c.4327C>G
Protein (HGVS p.)
NP_009225.1:p.(Arg1443Gly)
GRCh38
chr17:43082434 G>C
GRCh37
chr17:41234451 G>C

Gene diagram

Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.

BRCA1NM_007294.4
Fetching transcript structure from UCSC…
gnomAD v4.1 65 / 1,613,954 alleles AF 4.03e-05 · 0 homozygotes · FAF 3.67e-05
gnomAD v2.1 9 / 282,760 alleles AF 3.18e-05 · 0 homozygotes · FAF 2.29e-05

By genetic ancestry

gnomAD v4.1

AF 4e-05 · 65 / 1,613,954 alleles · 0 hom · FAF 3.7e-05
Admixed American5 / 59,986 8.3e-05
European (non-Finnish)55 / 1,179,998 4.7e-05
African/African American3 / 74,910 4e-05
Remaining individuals2 / 62,486 3.2e-05
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 3.2e-05 · 9 / 282,760 alleles · 0 hom · FAF 2.3e-05
Remaining individuals1 / 7,216 0.00014
Admixed American2 / 35,428 5.6e-05
European (non-Finnish)6 / 129,108 4.6e-05
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 4.02738e-05; MAF= 0.00403%, 65/1613954 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.33528e-05; MAF= 0.00834%, 5/59986 alleles, homozygotes = 0); grpmax FAF= 3.666e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.18291e-05; MAF= 0.00318%, 9/282760 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138581; MAF= 0.01386%, 1/7216 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

PP3 Computational evidence does not support a damaging effect. BayesDel no-AF is -0.285466, below the BRCA1 PP3 threshold of 0.28, and SpliceAI predicts no significant splice impact with a max delta score of 0.01, below the PP3 splice threshold of 0.2. REVEL is also low at 0.007. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP3 rule
Evidence considered
  • BayesDel no-AF -0.285466
  • SpliceAI max delta score 0.01
  • REVEL 0.007
Sources
cspec ↗spliceai ↗bayesdelrevel
BP4 Available computational evidence is benign-leaning, but the BRCA1 BP4 rule is restricted to missense variants inside a clinically important functional domain with BayesDel no-AF 0.15 or lower and SpliceAI 0.1 or lower. This variant is outside those domains, so BP4 is not applied here. BayesDel is -0.285466, SpliceAI max delta score is 0.01, and REVEL is 0.007; this benign computational profile is captured by BP1_Strong rather than BP4. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP4 rule
Evidence considered
  • Variant is outside ENIGMA BRCA1 functional domains
  • BayesDel no-AF -0.285466
  • SpliceAI max delta score 0.01
  • REVEL 0.007
Sources
cspec ↗vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel
BP7 No reviewed RNA study showed a normal transcript profile for this variant, so BP7 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP7 rule
Evidence considered
  • BRCA1 VCEP BP7 requires transcript-level evidence or qualifying silent/intronic context
Still missing
  • No variant-specific mRNA assay result was identified.
Sources
cspec ↗spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.007. BayesDel score = -0.285466.

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

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

gnomAD v4.1 65 / 1,613,954 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Captured SpliceAI source record Open source ↗
ClinVar Captured ClinVar source record 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

This variant is present in gnomAD v4.1 (AF= 4.02738e-05; MAF= 0.00403%, 65/1613954 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.33528e-05; MAF= 0.00834%, 5/59986 alleles, homozygotes = 0); grpmax FAF= 3.666e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.18291e-05; MAF= 0.00318%, 9/282760 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000138581; MAF= 0.01386%, 1/7216 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.

ClinVar

This variant has been reported in ClinVar as Likely benign (8 clinical laboratories) and as Benign (6 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel).

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.007. BayesDel score = -0.285466.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

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.