7-87600124-T-C

Position:

chr7-87600124-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001348946.2(ABCB1):c.61A>G(p.Asn21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,612,594 control chromosomes in the GnomAD database, including 8,366 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.071 ( 633 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7733 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.196

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015675128).

BP6

Variant 7-87600124-T-C is Benign according to our data. Variant chr7-87600124-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 829327.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB1	NM_001348946.2 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	2/28	ENST00000622132.5
ABCB1	NM_001348945.2 linkuse as main transcript	c.271A>G	p.Asn91Asp	missense_variant	6/32
ABCB1	NM_000927.5 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	3/29
ABCB1	NM_001348944.2 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	4/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	2/28	1	NM_001348946.2	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	3/29	1		P1	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	3/28	5			P08183-2
ABCB1	ENST00000416177.1 linkuse as main transcript	c.61A>G	p.Asn21Asp	missense_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0713

AC:

10852

AN:

152176

Hom.:

633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0250

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0731

AC:

18331

AN:

250642

Hom.:

1030

AF XY:

0.0741

AC XY:

10034

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0246

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.0685

GnomAD4 exome

AF:

0.0940

AC:

137226

AN:

1460300

Hom.:

7733

Cov.:

AF XY:

0.0922

AC XY:

66983

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.0757

GnomAD4 genome

AF:

0.0712

AC:

10849

AN:

152294

Hom.:

633

Cov.:

AF XY:

0.0718

AC XY:

5346

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.0397

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0873

Hom.:

1742

Bravo

AF:

0.0579

TwinsUK

AF:

0.103

AC:

382

ALSPAC

AF:

0.0991

AC:

382

ESP6500AA

AF:

0.0270

AC:

119

ESP6500EA

AF:

0.0997

AC:

857

ExAC

AF:

0.0758

AC:

9204

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ABCB1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

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

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.36

CADD

Benign

1.2

DANN

Benign

0.36

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.50

T;.;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.0020

B;B;.;.

Vest4

0.039

MPC

0.24

ClinPred

0.000071

GERP RS

-2.7

Varity_R

0.042

gMVP

0.068

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