7-87550882-C-T

Variant names:

• chr7-87550882-C-T
• rs10276036
• NM_001348946.2:c.1000-44G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.701
• Publications: 66 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.1000-44G>A		intron_variant	Intron 9 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.1210-44G>A		intron_variant	Intron 13 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.1000-44G>A		intron_variant	Intron 10 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.1000-44G>A		intron_variant	Intron 11 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.1000-44G>A		intron_variant	Intron 9 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.1000-44G>A		intron_variant	Intron 10 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.808-44G>A		intron_variant	Intron 9 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91584 AN: 151972 Hom.: 28416 Cov.: 33

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

GnomAD2 exomes AF: 0.533 AC: 129540 AN: 243236 AF XY: 0.525

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 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.: 15 AF XY: 0.541 AC XY: 306678 AN XY: 567310

African (AFR) AF: 0.764 AC: 20172 AN: 26404

American (AMR) AF: 0.511 AC: 22448 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 15360 AN: 23902

East Asian (EAS) AF: 0.376 AC: 14307 AN: 38040

South Asian (SAS) AF: 0.394 AC: 31008 AN: 78762

European-Finnish (FIN) AF: 0.518 AC: 26771 AN: 51652

Middle Eastern (MID) AF: 0.545 AC: 2779 AN: 5098

European-Non Finnish (NFE) AF: 0.563 AC: 445189 AN: 791260

Other (OTH) AF: 0.554 AC: 27026 AN: 48810

GnomAD4 genome AF: 0.603 AC: 91705 AN: 152088 Hom.: 28468 Cov.: 33 AF XY: 0.596 AC XY: 44345 AN XY: 74346

African (AFR) AF: 0.752 AC: 31193 AN: 41488

American (AMR) AF: 0.566 AC: 8655 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2198 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5176

South Asian (SAS) AF: 0.402 AC: 1938 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5419 AN: 10534

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38355 AN: 67990

Other (OTH) AF: 0.610 AC: 1289 AN: 2114

Alfa AF: 0.576 Hom.: 115767

Bravo AF: 0.614

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- 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
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10276036; hg19: chr7-87180198;