4-83485040-C-T

Variant names:

• chr4-83485040-C-T
• rs368088450
• NM_139076.3:c.33G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_139076.3(ABRAXAS1):​c.33G>A​(p.Ser11Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S11S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ABRAXAS1 NM_139076.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABRAXAS1	NM_139076.3	c.33G>A	p.Ser11Ser	synonymous_variant	Exon 1 of 9	ENST00000321945.12	NP_620775.2
ABRAXAS1	XR_001741334.3	n.61G>A		non_coding_transcript_exon_variant	Exon 1 of 9
ABRAXAS1	NM_001345962.2	c.-228G>A		5_prime_UTR_variant	Exon 1 of 8		NP_001332891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABRAXAS1	ENST00000321945.12	c.33G>A	p.Ser11Ser	synonymous_variant	Exon 1 of 9	1	NM_139076.3	ENSP00000369857.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443220 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718292

African (AFR) AF: 0.00 AC: 0 AN: 30988

American (AMR) AF: 0.00 AC: 0 AN: 43390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25584

East Asian (EAS) AF: 0.00 AC: 0 AN: 37796

South Asian (SAS) AF: 0.00 AC: 0 AN: 84294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103674

Other (OTH) AF: 0.00 AC: 0 AN: 59462

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.4
DANN	Benign	0.96
PhyloP100		-2.3
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs368088450; hg19: chr4-84406193; COSMIC: COSV58948738;