7-87531302-A-T

Position:

chr7-87531302-A-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_001348946.2(ABCB1):c.2677T>A(p.Ser893Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,612,540 control chromosomes in the GnomAD database, including 1,104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S893Y) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.024 ( 98 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1006 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 2.22

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 -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr7-87531301-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1164001.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018371046).

BP6

Variant 7-87531302-A-T is Benign according to our data. Variant chr7-87531302-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 166619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCB1	NM_001348946.2 linkuse as main transcript	c.2677T>A	p.Ser893Thr	missense_variant	21/28	ENST00000622132.5
ABCB1	NM_001348945.2 linkuse as main transcript	c.2887T>A	p.Ser963Thr	missense_variant	25/32
ABCB1	NM_000927.5 linkuse as main transcript	c.2677T>A	p.Ser893Thr	missense_variant	22/29
ABCB1	NM_001348944.2 linkuse as main transcript	c.2677T>A	p.Ser893Thr	missense_variant	23/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.2677T>A	p.Ser893Thr	missense_variant	21/28	1	NM_001348946.2	P1	P08183-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3636

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00444

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0500

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0377

AC:

9446

AN:

250640

Hom.:

302

AF XY:

0.0366

AC XY:

4959

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.00419

Gnomad AMR exome

AF:

0.0540

Gnomad ASJ exome

AF:

0.0263

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.0428

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0350

GnomAD4 exome

AF:

0.0266

AC:

38819

AN:

1460416

Hom.:

1006

Cov.:

AF XY:

0.0270

AC XY:

19614

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.00305

Gnomad4 AMR exome

AF:

0.0522

Gnomad4 ASJ exome

AF:

0.0250

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.0444

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0199

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0239

AC:

3634

AN:

152124

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1888

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00443

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0262

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.0492

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0214

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.00125

Hom.:

42212

TwinsUK

AF:

0.0205

AC:

ALSPAC

AF:

0.0176

AC:

ExAC

AF:

0.0371

AC:

4507

EpiCase

AF:

0.0207

EpiControl

AF:

0.0216

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 06, 2014

- -

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). -

Ovarian neoplasm

Other:1

not provided, no classification provided

literature only

Database of Curated Mutations (DoCM)

Mar 10, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.55

T;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.9

M;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.027

.;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.0010

B;B;.

Vest4

0.088

MPC

0.25

ClinPred

0.018

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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