rs2032582

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1

The NM_001348946.2(ABCB1):c.2677T>G(p.Ser893Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,611,172 control chromosomes in the GnomAD database, including 250,710 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 0.64 ( 33550 hom., cov: 32)

Exomes 𝑓: 0.54 ( 217160 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:2

Conservation

PhyloP100: 2.22

Publications

1557 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1164001.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=9.965592E-7).

BP6

Variant 7-87531302-A-C is Benign according to our data. Variant chr7-87531302-A-C is described in ClinVar as Benign. ClinVar VariationId is 166622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2 link	c.2677T>G	p.Ser893Ala	missense_variant	Exon 21 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.2887T>G	p.Ser963Ala	missense_variant	Exon 25 of 32		NP_001335874.1
ABCB1	NM_000927.5 link	c.2677T>G	p.Ser893Ala	missense_variant	Exon 22 of 29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 link	c.2677T>G	p.Ser893Ala	missense_variant	Exon 23 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 link	c.2677T>G	p.Ser893Ala	missense_variant	Exon 21 of 28	1	NM_001348946.2	ENSP00000478255.1		P08183-1

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97433

AN:

151960

Hom.:

33483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.910

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.647

GnomAD2 exomes

AF:

0.539

AC:

135082

AN:

250640

AF XY:

0.524

show subpopulations

Gnomad AFR exome

AF:

0.918

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.549

Gnomad OTH exome

AF:

0.548

GnomAD4 exome

AF:

0.539

AC:

786633

AN:

1459094

Hom.:

217160

Cov.:

AF XY:

0.532

AC XY:

386422

AN XY:

725932

show subpopulations

African (AFR)

AF:

0.926

AC:

30932

AN:

33402

American (AMR)

AF:

0.549

AC:

24522

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.633

AC:

16508

AN:

26092

East Asian (EAS)

AF:

0.442

AC:

17501

AN:

39598

South Asian (SAS)

AF:

0.350

AC:

30155

AN:

86212

European-Finnish (FIN)

AF:

0.475

AC:

25288

AN:

53202

Middle Eastern (MID)

AF:

0.560

AC:

3216

AN:

5744

European-Non Finnish (NFE)

AF:

0.545

AC:

604939

AN:

1109954

Other (OTH)

AF:

0.557

AC:

33572

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

17607

35213

52820

70426

88033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17074

34148

51222

68296

85370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.642

AC:

97571

AN:

152078

Hom.:

33550

Cov.:

AF XY:

0.634

AC XY:

47095

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.911

AC:

37810

AN:

41526

American (AMR)

AF:

0.604

AC:

9216

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

2180

AN:

3470

East Asian (EAS)

AF:

0.474

AC:

2449

AN:

5170

South Asian (SAS)

AF:

0.358

AC:

1723

AN:

4818

European-Finnish (FIN)

AF:

0.476

AC:

5029

AN:

10574

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37091

AN:

67942

Other (OTH)

AF:

0.643

AC:

1359

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1594

3189

4783

6378

7972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.561

Hom.:

60461

Bravo

AF:

0.679

TwinsUK

AF:

0.551

AC:

2042

ALSPAC

AF:

0.554

AC:

2136

ESP6500AA

AF:

0.892

AC:

3930

ESP6500EA

AF:

0.568

AC:

4889

ExAC

AF:

0.543

AC:

65897

EpiCase

AF:

0.543

EpiControl

AF:

0.545

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 27, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABCB1-related disorder

Benign:1

Jul 21, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Inflammatory bowel disease 13

Other:1

Dec 01, 2003

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:research

- 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

0.050

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.33

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.23

T;.;T

MetaRNN

Benign

0.0000010

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.0

N;N;.

PhyloP100

2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

1.7

.;N;N

REVEL

Benign

0.28

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.043

MPC

0.17

ClinPred

0.0027

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.27

gMVP

0.54

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over