Variant 7-87550882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001348946.2(ABCB1):c.1000-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,259,928 control chromosomes in the GnomAD database, including 196,874 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 0.60 ( 28468 hom., cov: 33)

Exomes 𝑓: 0.55 ( 168406 hom. )

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.701

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ABCB1	NM_001348946.2 linkuse as main transcript	c.1000-44G>A	intron_variant	ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5 linkuse as main transcript	c.1000-44G>A	intron_variant		NP_000918.2
ABCB1	NM_001348944.2 linkuse as main transcript	c.1000-44G>A	intron_variant		NP_001335873.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.1210-44G>A	intron_variant		NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.1000-44G>A	intron_variant	1	NM_001348946.2	ENSP00000478255	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.1000-44G>A	intron_variant	1		ENSP00000265724	P1	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.808-44G>A	intron_variant	5		ENSP00000444095		P08183-2

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91584

AN:

151972

Hom.:

28416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.633

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.514

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.612

GnomAD3 exomes

AF:

0.533

AC:

129540

AN:

243236

Hom.:

35511

AF XY:

0.525

AC XY:

69284

AN XY:

132082

show subpopulations

Gnomad AFR exome

AF:

0.755

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.359

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.546

AC:

605060

AN:

1107840

Hom.:

168406

Cov.:

AF XY:

0.541

AC XY:

306678

AN XY:

567310

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.376

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.563

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.603

AC:

91705

AN:

152088

Hom.:

28468

Cov.:

AF XY:

0.596

AC XY:

44345

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.633

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.514

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.571

Hom.:

54408

Bravo

AF:

0.614

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

-0.92

CADD

Benign

0.30

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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