Variant 16-16079375-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_004996.4(ABCC1):c.2012G>T(p.Gly671Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,613,958 control chromosomes in the GnomAD database, including 1,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.036 ( 131 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1826 hom. )

Consequence

ABCC1
NM_004996.4 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The protein encoded by this gene is a member of 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 full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0040707886).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4 linkuse as main transcript	c.2012G>T	p.Gly671Val	missense_variant	16/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8 linkuse as main transcript	c.2012G>T	p.Gly671Val	missense_variant	16/31	1	NM_004996.4	P1	P33527-1

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5449

AN:

152128

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0380

AC:

9480

AN:

249312

Hom.:

258

AF XY:

0.0388

AC XY:

5253

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0323

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.0604

Gnomad NFE exome

AF:

0.0562

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0477

AC:

69742

AN:

1461712

Hom.:

1826

Cov.:

AF XY:

0.0471

AC XY:

34222

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00875

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0168

Gnomad4 FIN exome

AF:

0.0604

Gnomad4 NFE exome

AF:

0.0542

Gnomad4 OTH exome

AF:

0.0432

GnomAD4 genome

AF:

0.0358

AC:

5446

AN:

152246

Hom.:

131

Cov.:

AF XY:

0.0343

AC XY:

2553

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0505

Gnomad4 NFE

AF:

0.0536

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0482

Hom.:

342

Bravo

AF:

0.0337

TwinsUK

AF:

0.0553

AC:

205

ALSPAC

AF:

0.0529

AC:

204

ESP6500AA

AF:

0.0119

AC:

ESP6500EA

AF:

0.0559

AC:

473

ExAC

AF:

0.0392

AC:

4744

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0546

EpiControl

AF:

0.0544

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Atorvastatin response

Other:1

drug response, no assertion criteria provided

in vitro

Pharmacometrics, Pharmacogenomics, Pharmacokinetics Research Group, Catholic University of Louvain

Apr 13, 2022

functional variant -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0041

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

4.5

H;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-7.8

D;.

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.71

MPC

1.2

ClinPred

0.10

GERP RS

4.8

Varity_R

0.98

gMVP

0.97

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