4-83485052-C-T

Variant names:

• chr4-83485052-C-T
• rs145796091
• NM_139076.3:c.21G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_139076.3(ABRAXAS1):​c.21G>A​(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,593,722 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S7S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0068 (36 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (145 hom.)
• Consequence: ABRAXAS1 NM_139076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.272
• Publications: 3 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-83485052-C-T is Benign according to our data. Variant chr4-83485052-C-T is described in ClinVar as Benign. ClinVar VariationId is 416711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.272 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139076.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	NM_139076.3	MANE Select	c.21G>A	p.Ser7Ser	synonymous	Exon 1 of 9	NP_620775.2	Q6UWZ7-1
	ABRAXAS1	NM_001345962.2		c.-240G>A		5_prime_UTR	Exon 1 of 8	NP_001332891.1	Q6UWZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABRAXAS1	ENST00000321945.12	TSL:1 MANE Select	c.21G>A	p.Ser7Ser	synonymous	Exon 1 of 9	ENSP00000369857.3	Q6UWZ7-1
	ABRAXAS1	ENST00000515303.2	TSL:1	c.-131G>A		5_prime_UTR	Exon 1 of 3	ENSP00000421068.1	E9PHB9
	ABRAXAS1	ENST00000856950.1		c.21G>A	p.Ser7Ser	synonymous	Exon 1 of 9	ENSP00000527009.1

Frequencies

GnomAD3 genomes AF: 0.00688 AC: 1047 AN: 152180 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0114 AC: 2625 AN: 229328 AF XY: 0.00860

Gnomad AFR exome AF: 0.000336

Gnomad AMR exome AF: 0.0720

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.0155

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000669

Gnomad OTH exome AF: 0.00748

GnomAD4 exome AF: 0.00265 AC: 3823 AN: 1441434 Hom.: 145 Cov.: 30 AF XY: 0.00225 AC XY: 1615 AN XY: 717386

African (AFR) AF: 0.000389 AC: 12 AN: 30862

American (AMR) AF: 0.0698 AC: 3015 AN: 43188

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25522

East Asian (EAS) AF: 0.0130 AC: 488 AN: 37550

South Asian (SAS) AF: 0.000666 AC: 56 AN: 84106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52362

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5694

European-Non Finnish (NFE) AF: 0.0000499 AC: 55 AN: 1102754

Other (OTH) AF: 0.00325 AC: 193 AN: 59396

GnomAD4 genome AF: 0.00684 AC: 1042 AN: 152288 Hom.: 36 Cov.: 33 AF XY: 0.00803 AC XY: 598 AN XY: 74464

African (AFR) AF: 0.000481 AC: 20 AN: 41580

American (AMR) AF: 0.0592 AC: 905 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5170

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68000

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00115 Hom.: 3

Bravo AF: 0.0113

Asia WGS AF: 0.0110 AC: 37 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ABRAXAS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.7
DANN	Benign	0.86
PhyloP100		0.27
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=296/4	polymorphism (auto)

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: rs145796091; hg19: chr4-84406205; COSMIC: COSV58949686;