rs1128503

Positions:

chr7-87550285-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001348946.2(ABCB1):c.1236T>C(p.Gly412=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,758 control chromosomes in the GnomAD database, including 256,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30325 hom., cov: 32)

Exomes 𝑓: 0.55 ( 226668 hom. )

Consequence

ABCB1
NM_001348946.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.153

Variant links:

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated 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 protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ABCB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-87550285-A-G is Benign according to our data. Variant chr7-87550285-A-G is described in ClinVar as [Benign]. Clinvar id is 194187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87550285-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABCB1	NM_001348946.2 linkuse as main transcript	c.1236T>C	p.Gly412=	synonymous_variant	12/28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.1446T>C	p.Gly482=	synonymous_variant	16/32		NP_001335874.1
ABCB1	NM_000927.5 linkuse as main transcript	c.1236T>C	p.Gly412=	synonymous_variant	13/29		NP_000918.2
ABCB1	NM_001348944.2 linkuse as main transcript	c.1236T>C	p.Gly412=	synonymous_variant	14/30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.1236T>C	p.Gly412=	synonymous_variant	12/28	1	NM_001348946.2	ENSP00000478255	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.1236T>C	p.Gly412=	synonymous_variant	13/29	1		ENSP00000265724	P1	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.1044T>C	p.Gly348=	synonymous_variant	12/28	5		ENSP00000444095		P08183-2

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

93943

AN:

151856

Hom.:

30269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.622

GnomAD3 exomes

AF:

0.537

AC:

134826

AN:

251258

Hom.:

37666

AF XY:

0.527

AC XY:

71570

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.811

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.552

GnomAD4 exome

AF:

0.553

AC:

807661

AN:

1461784

Hom.:

226668

Cov.:

AF XY:

0.547

AC XY:

397991

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.822

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.376

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.619

AC:

94069

AN:

151974

Hom.:

30325

Cov.:

AF XY:

0.612

AC XY:

45432

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.807

Gnomad4 AMR

AF:

0.574

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.619

Alfa

AF:

0.577

Hom.:

54035

Bravo

AF:

0.632

Asia WGS

AF:

0.429

AC:

1498

AN:

3478

EpiCase

AF:

0.561

EpiControl

AF:

0.563

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 13, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 06, 2014

- -

ABCB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 21, 2021

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). -

Tramadol response

Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.3

DANN

Benign

0.45

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