Variant 16-16007952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004996.4(ABCC1):c.185G>A(p.Arg62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,568,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

ABCC1
NM_004996.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.79

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007705897).

BP6

Variant 16-16007952-G-A is Benign according to our data. Variant chr16-16007952-G-A is described in ClinVar as [Benign]. Clinvar id is 3049946.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/31	1	NM_004996.4	P1	P33527-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

214

AN:

148094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000299

AC:

AN:

244136

Hom.:

AF XY:

0.000211

AC XY:

AN XY:

132488

show subpopulations

Gnomad AFR exome

AF:

0.00421

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

179

AN:

1419818

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

705926

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000472

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.000260

GnomAD4 genome

AF:

0.00145

AC:

215

AN:

148212

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

106

AN XY:

72162

show subpopulations

Gnomad4 AFR

AF:

0.00507

Gnomad4 AMR

AF:

0.000543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000298

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.00168

ESP6500AA

AF:

0.00418

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000405

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000604

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ABCC1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 16, 2020

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

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.98

N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.051

Sift

Benign

0.22

Sift4G

Benign

0.18

Polyphen

0.051

Vest4

0.30

MVP

0.45

MPC

0.40

ClinPred

0.0046

GERP RS

4.0

Varity_R

0.044

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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