Variant rs2235033 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.1554+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,612,890 control chromosomes in the GnomAD database, including 185,247 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 0.48 ( 17444 hom., cov: 32)

Exomes 𝑓: 0.48 ( 167803 hom. )

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -1.45

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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ABCB1	NM_001348946.2 linkuse as main transcript	c.1554+24T>C	intron_variant	ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5 linkuse as main transcript	c.1554+24T>C	intron_variant		NP_000918.2
ABCB1	NM_001348944.2 linkuse as main transcript	c.1554+24T>C	intron_variant		NP_001335873.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.1764+24T>C	intron_variant		NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.1554+24T>C	intron_variant	1	NM_001348946.2	ENSP00000478255	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.1554+24T>C	intron_variant	1		ENSP00000265724	P1	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.1362+24T>C	intron_variant	5		ENSP00000444095		P08183-2
ABCB1	ENST00000482527.1 linkuse as main transcript	n.308+24T>C	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72601

AN:

151920

Hom.:

17424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.508

GnomAD3 exomes

AF:

0.460

AC:

115567

AN:

251234

Hom.:

27188

AF XY:

0.456

AC XY:

61925

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.358

Gnomad SAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.477

AC:

696742

AN:

1460852

Hom.:

167803

Cov.:

AF XY:

0.474

AC XY:

344757

AN XY:

726786

show subpopulations

Gnomad4 AFR exome

AF:

0.481

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.491

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.478

AC:

72665

AN:

152038

Hom.:

17444

Cov.:

AF XY:

0.473

AC XY:

35166

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.506

Alfa

AF:

0.495

Hom.:

40710

Bravo

AF:

0.487

Asia WGS

AF:

0.391

AC:

1361

AN:

3476

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

-0.80

CADD

Benign

2.5

DANN

Benign

0.46

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

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