rs9282564

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,drug response (no stars).

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; drug response no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.196

Publications

136 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 -13 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|drug_response. ClinVar VariationId is 829327.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348946.2	MANE Select	c.61A>G	p.Asn21Asp	missense	Exon 2 of 28	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.271A>G	p.Asn91Asp	missense	Exon 6 of 32	NP_001335874.1
ABCB1	NM_000927.5		c.61A>G	p.Asn21Asp	missense	Exon 3 of 29	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.61A>G	p.Asn21Asp	missense	Exon 2 of 28	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.61A>G	p.Asn21Asp	missense	Exon 3 of 29	ENSP00000265724.3	P08183-1
ABCB1	ENST00000890305.1		c.61A>G	p.Asn21Asp	missense	Exon 1 of 27	ENSP00000560364.1

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

GnomAD2 exomes

AF:

0.0731

AC:

18331

AN:

250642

AF XY:

0.0741

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 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

African (AFR)

AF:

0.0133

AC:

445

AN:

33462

American (AMR)

AF:

0.0302

AC:

1348

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0232

AC:

605

AN:

26130

East Asian (EAS)

AF:

0.000151

AC:

AN:

39692

South Asian (SAS)

AF:

0.0257

AC:

2217

AN:

86180

European-Finnish (FIN)

AF:

0.169

AC:

9024

AN:

53372

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.107

AC:

118956

AN:

1110670

Other (OTH)

AF:

0.0757

AC:

4567

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5717

11434

17151

22868

28585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4148

8296

12444

16592

20740

<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:

0.0712

AC:

10849

AN:

152294

Hom.:

633

Cov.:

AF XY:

0.0718

AC XY:

5346

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0158

AC:

657

AN:

41568

American (AMR)

AF:

0.0397

AC:

608

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0251

AC:

121

AN:

4828

European-Finnish (FIN)

AF:

0.176

AC:

1863

AN:

10602

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7349

AN:

68014

Other (OTH)

AF:

0.0473

AC:

100

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

518

1036

1554

2072

2590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0867

Hom.:

3257

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

ClinVar submissions

Significance:Likely benign; drug response

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ABCB1-related disorder (1)

Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.36

CADD

Benign

1.2

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.052

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.20

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.49

REVEL

Benign

0.17

Sift

Benign

0.50

Sift4G

Benign

0.67

Polyphen

0.0020

Vest4

0.039

MPC

0.24

ClinPred

0.000071

GERP RS

-2.7

Varity_R

0.042

gMVP

0.068

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over