About BRCA1
No gene-level summary was recorded for this case.
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.No gene-level summary was recorded for this case.
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.
The applied criteria and their strengths are shown as assessed under the stated framework.
This variant is absent from gnomAD v2.1 (non-cancer, exome only) and gnomAD v4.1 (non-cancer), meeting ENIGMA PM2_Supporting. The variant is absent from all outbred population controls in these databases.
This missense variant (p.Ser1484Ala) is located at amino acid position 1484, which lies outside all ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT repeats aa 1650-1857). SpliceAI predicts no splicing impact (max delta score = 0.03, ≤0.1). This meets ENIGMA BP1_Strong per the specification: missense variant outside a clinically important functional domain AND no splicing predicted.
ENIGMA BRCA1 v1.2.0 point system for conflicting evidence: PM2_Supporting (+1 pathogenic) + BP1_Strong (-4 benign) = -3 total points. Range -6 to -2 = Likely Benign.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1 allele counts were not recorded for this variant.
Absent from gnomAD v2.1.
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
3 Uncertain significance.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under ClinGen BRCA1 VCEP v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 14 not met · 0 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
NM_007294.4:c.4450T>G (p.Ser1484Ala) is a missense variant in BRCA1 exon 13 located at amino acid position 1484, outside all ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT repeats aa 1650-1857). SpliceAI predicts no splicing impact (max delta 0.03).
This variant is absent from gnomAD v2.1 and v4.1 population databases, meeting ENIGMA PM2_Supporting.
The variant meets ENIGMA BP1_Strong: missense variant outside a clinically important functional domain with no predicted splicing impact (SpliceAI max delta 0.03 ≤0.1).
This variant is not listed in ENIGMA Table9 (curated functional assays) or ST4 (functional assay results) for either PS3 or BS3. The related variant c.4450T>A (p.Ser1484Thr) has BS3_Strong with 'No functional impact,' but this is a different amino acid substitution and does not constitute direct evidence for p.Ser1484Ala.
No case-control, segregation, or clinical-history likelihood ratio data were identified for this specific variant. It is not listed in the Li et al. 2020 (PMID:31853058) clinical-history LR table; c.4450T>A is listed with neutral LR=1.066.
In ClinVar, this variant is classified as Uncertain Significance by three clinical laboratories (ClinVar ID 630099). No expert panel classification is available.
Under the ENIGMA Table 3 all_of combination rules, one Strong Benign criterion (BP1_Strong) with no qualifying Supporting Benign or Moderate Benign criterion does not meet the Likely Benign threshold (requires Strong Benign + Supporting Benign or Strong Benign + Moderate Benign). The conflicting PM2_Supporting (pathogenic direction) further precludes a benign or likely benign classification. The variant remains a Variant of Uncertain Significance.
No criteria match.
Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.15. BayesDel score = -0.314566.
9 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.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
Absent from gnomAD v4.1.
Absent from gnomAD v2.1.
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories). (ClinVarID = 630099)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.15. BayesDel score = -0.314566.
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.