Variant 7-87595730-G-A 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.117+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,516,832 control chromosomes in the GnomAD database, including 1,890 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 0.063 ( 390 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1500 hom. )

Consequence

ABCB1
NM_001348946.2 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.518

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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ABCB1	NM_001348946.2 linkuse as main transcript	c.117+36C>T	intron_variant	ENST00000622132.5
ABCB1	NM_000927.5 linkuse as main transcript	c.117+36C>T	intron_variant
ABCB1	NM_001348944.2 linkuse as main transcript	c.117+36C>T	intron_variant
ABCB1	NM_001348945.2 linkuse as main transcript	c.327+36C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.117+36C>T	intron_variant	1	NM_001348946.2	P1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.117+36C>T	intron_variant	1		P1	P08183-1
ABCB1	ENST00000416177.1 linkuse as main transcript	c.117+36C>T	intron_variant	5
ABCB1	ENST00000543898.5 linkuse as main transcript	c.117+36C>T	intron_variant	5			P08183-2

Frequencies

GnomAD3 genomes

AF:

0.0623

AC:

9461

AN:

151802

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0671

GnomAD3 exomes

AF:

0.0430

AC:

10674

AN:

248138

Hom.:

324

AF XY:

0.0409

AC XY:

5487

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0384

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.0469

Gnomad SAS exome

AF:

0.0272

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0394

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0425

AC:

58040

AN:

1364912

Hom.:

1500

Cov.:

AF XY:

0.0418

AC XY:

28600

AN XY:

684114

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0399

Gnomad4 ASJ exome

AF:

0.0264

Gnomad4 EAS exome

AF:

0.0603

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.0625

AC:

9498

AN:

151920

Hom.:

390

Cov.:

AF XY:

0.0609

AC XY:

4521

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.0507

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0674

Alfa

AF:

0.0430

Hom.:

216

Bravo

AF:

0.0650

Asia WGS

AF:

0.0460

AC:

163

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

-0.83

CADD

Benign

5.4

DANN

Benign

0.80

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