4-88097518-C-T

Position:

chr4-88097518-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004827.3(ABCG2):c.1582G>A(p.Ala528Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00163 in 1,614,190 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ABCG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0121077895).

BP6

Variant 4-88097518-C-T is Benign according to our data. Variant chr4-88097518-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041649.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_004827.3 linkuse as main transcript	c.1582G>A	p.Ala528Thr	missense_variant	13/16	ENST00000237612.8	NP_004818.2	Q9UNQ0-1A1LUE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCG2	ENST00000237612.8 linkuse as main transcript	c.1582G>A	p.Ala528Thr	missense_variant	13/16	1	NM_004827.3	ENSP00000237612.3	Q9UNQ0-1
ABCG2	ENST00000515655.5 linkuse as main transcript	c.1582G>A	p.Ala528Thr	missense_variant	13/16	1		ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000650821.1 linkuse as main transcript	c.1582G>A	p.Ala528Thr	missense_variant	14/17			ENSP00000498246.1	Q9UNQ0-1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00152

AC:

383

AN:

251258

Hom.:

AF XY:

0.00155

AC XY:

210

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00963

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00167

AC:

2434

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1189

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00987

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00175

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152348

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00139

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00143

AC:

174

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ABCG2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2022

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

0.60

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T

Eigen

Benign

0.071

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.26

Sift

Benign

0.24

T;T

Sift4G

Benign

0.069

T;D

Polyphen

0.17

B;B

Vest4

0.71

MVP

0.67

MPC

0.036

ClinPred

0.018

GERP RS

5.5

Varity_R

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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