4-83484979-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_139076.3(ABRAXAS1):​c.87+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ABRAXAS1
NM_139076.3 splice_region, intron

Scores

1
7
Splicing: ADA: 0.07966
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.902
Variant links:
Genes affected
ABRAXAS1 (HGNC:25829): (abraxas 1, BRCA1 A complex subunit) This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19163531).
BP6
Variant 4-83484979-G-C is Benign according to our data. Variant chr4-83484979-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1651214.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABRAXAS1NM_139076.3 linkuse as main transcriptc.87+7C>G splice_region_variant, intron_variant ENST00000321945.12 NP_620775.2
ABRAXAS1NM_001345962.2 linkuse as main transcriptc.-174+7C>G splice_region_variant, intron_variant NP_001332891.1
ABRAXAS1XR_001741334.3 linkuse as main transcriptn.115+7C>G splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABRAXAS1ENST00000321945.12 linkuse as main transcriptc.87+7C>G splice_region_variant, intron_variant 1 NM_139076.3 ENSP00000369857 P1Q6UWZ7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 29, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
13
DANN
Benign
0.91
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.29
T
MetaRNN
Benign
0.19
T
MutationTaster
Benign
1.0
D;D;D
Sift4G
Uncertain
0.023
D
MVP
0.58
GERP RS
3.3

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.080
dbscSNV1_RF
Benign
0.21
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84406132; API