Variant rs2032588 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000622132.5(ABCB1):c.1350+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,930 control chromosomes in the GnomAD database, including 4,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.094 ( 1001 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3241 hom. )

Consequence

ABCB1
ENST00000622132.5 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.336

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ABCB1	NM_001348946.2 linkuse as main transcript	c.1350+44C>T	intron_variant	ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5 linkuse as main transcript	c.1350+44C>T	intron_variant		NP_000918.2
ABCB1	NM_001348944.2 linkuse as main transcript	c.1350+44C>T	intron_variant		NP_001335873.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.1560+44C>T	intron_variant		NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.1350+44C>T	intron_variant		1	NM_001348946.2	ENSP00000478255	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.1350+44C>T	intron_variant		1		ENSP00000265724	P1	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.1158+44C>T	intron_variant		5		ENSP00000444095		P08183-2
ABCB1	ENST00000482527.1 linkuse as main transcript	n.32C>T	non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.0937

AC:

14256

AN:

152116

Hom.:

996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0498

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0586

Gnomad OTH

AF:

0.0813

GnomAD3 exomes

AF:

0.0555

AC:

13956

AN:

251310

Hom.:

726

AF XY:

0.0517

AC XY:

7026

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.0300

Gnomad ASJ exome

AF:

0.0630

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00572

Gnomad FIN exome

AF:

0.0910

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.0581

GnomAD4 exome

AF:

0.0584

AC:

85421

AN:

1461696

Hom.:

3241

Cov.:

AF XY:

0.0563

AC XY:

40915

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0319

Gnomad4 ASJ exome

AF:

0.0637

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00582

Gnomad4 FIN exome

AF:

0.0913

Gnomad4 NFE exome

AF:

0.0591

Gnomad4 OTH exome

AF:

0.0625

GnomAD4 genome

AF:

0.0939

AC:

14290

AN:

152234

Hom.:

1001

Cov.:

AF XY:

0.0922

AC XY:

6863

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.0496

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0953

Gnomad4 NFE

AF:

0.0586

Gnomad4 OTH

AF:

0.0810

Alfa

AF:

0.0722

Hom.:

178

Bravo

AF:

0.0965

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

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

-0.84

CADD

Benign

0.44

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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