4-83470257-G-A

Position:

chr4-83470257-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_139076.3(ABRAXAS1):c.422C>T(p.Thr141Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,613,660 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 45 hom. )

Consequence

ABRAXAS1
NM_139076.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009476125).

BP6

Variant 4-83470257-G-A is Benign according to our data. Variant chr4-83470257-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 128222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83470257-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABRAXAS1	NM_139076.3 linkuse as main transcript	c.422C>T	p.Thr141Ile	missense_variant	5/9	ENST00000321945.12
ABRAXAS1	NM_001345962.2 linkuse as main transcript	c.95C>T	p.Thr32Ile	missense_variant	4/8
ABRAXAS1	XR_001741334.3 linkuse as main transcript	n.450C>T		non_coding_transcript_exon_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABRAXAS1	ENST00000321945.12 linkuse as main transcript	c.422C>T	p.Thr141Ile	missense_variant	5/9	1	NM_139076.3	P1	Q6UWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

698

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00740

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00388

AC:

973

AN:

250998

Hom.:

AF XY:

0.00362

AC XY:

491

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00633

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00702

AC:

10259

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

4906

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.00841

Gnomad4 OTH exome

AF:

0.00741

GnomAD4 genome

AF:

0.00459

AC:

698

AN:

152232

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00740

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00671

Hom.:

Bravo

AF:

0.00485

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00381

AC:

463

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00714

EpiControl

AF:

0.00510

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 19, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ABRAXAS1: BS1, BS2 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 11, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

ABRAXAS1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as likely 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

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.0095

T;T;T;T

MetaSVM

Benign

-0.50

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.9

D;D;.;.

REVEL

Uncertain

0.44

Sift

Uncertain

0.0010

D;D;.;.

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.56

MVP

0.67

MPC

0.53

ClinPred

0.017

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.70

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