Variant rs145796091 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139076.3(ABRAXAS1):c.21G>A(p.Ser7=) 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 (★★).

Frequency

Genomes: 𝑓 0.0068 ( 36 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 145 hom. )

Consequence

ABRAXAS1
NM_139076.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.272

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]

ABRAXAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 416711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83485052-C-T is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABRAXAS1	NM_139076.3 linkuse as main transcript	c.21G>A	p.Ser7=	synonymous_variant	1/9	ENST00000321945.12	NP_620775.2
ABRAXAS1	NM_001345962.2 linkuse as main transcript	c.-240G>A		5_prime_UTR_variant	1/8		NP_001332891.1
ABRAXAS1	XR_001741334.3 linkuse as main transcript	n.49G>A		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABRAXAS1	ENST00000321945.12 linkuse as main transcript	c.21G>A	p.Ser7=	synonymous_variant	1/9	1	NM_139076.3	ENSP00000369857	P1	Q6UWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152180

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0114

AC:

2625

AN:

229328

Hom.:

103

AF XY:

0.00860

AC XY:

1086

AN XY:

126296

show subpopulations

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 SAS exome

AF:

0.000558

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.:

AF XY:

0.00225

AC XY:

1615

AN XY:

717386

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.0698

Gnomad4 ASJ exome

AF:

0.0000392

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.000666

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000499

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00684

AC:

1042

AN:

152288

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

598

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.0592

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.0110

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

ABRAXAS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.7

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over