chr7-87549310-C-T

Variant names:

• chr7-87549310-C-T
• rs2235013
• NM_001348946.2:c.1725+38G>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.1725+38G>A 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 1,612,476 control chromosomes in the GnomAD database, including 185,124 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 (17440 hom., cov: 32)
  • Exomes 𝑓: 0.48 (167684 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.179
• Publications: 49 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.1725+38G>A		intron_variant	Intron 14 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.1935+38G>A		intron_variant	Intron 18 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.1725+38G>A		intron_variant	Intron 15 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.1725+38G>A		intron_variant	Intron 16 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.1725+38G>A		intron_variant	Intron 14 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.1725+38G>A		intron_variant	Intron 15 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.1533+38G>A		intron_variant	Intron 14 of 27	5		ENSP00000444095.1
ABCB1	ENST00000482527.1	n.479+38G>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72594 AN: 151922 Hom.: 17420 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.508

GnomAD2 exomes AF: 0.459 AC: 114654 AN: 249540 AF XY: 0.456

Gnomad AFR exome AF: 0.481

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.358

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.477 AC: 696533 AN: 1460434 Hom.: 167684 Cov.: 34 AF XY: 0.474 AC XY: 344613 AN XY: 726496

African (AFR) AF: 0.481 AC: 16085 AN: 33462

American (AMR) AF: 0.472 AC: 21051 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14795 AN: 26124

East Asian (EAS) AF: 0.378 AC: 14977 AN: 39674

South Asian (SAS) AF: 0.379 AC: 32671 AN: 86188

European-Finnish (FIN) AF: 0.389 AC: 20748 AN: 53350

Middle Eastern (MID) AF: 0.464 AC: 2676 AN: 5766

European-Non Finnish (NFE) AF: 0.491 AC: 545076 AN: 1110956

Other (OTH) AF: 0.472 AC: 28454 AN: 60344

GnomAD4 genome AF: 0.478 AC: 72659 AN: 152042 Hom.: 17440 Cov.: 32 AF XY: 0.473 AC XY: 35162 AN XY: 74310

African (AFR) AF: 0.484 AC: 20089 AN: 41494

American (AMR) AF: 0.506 AC: 7735 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1860 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4009 AN: 10536

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33380 AN: 67950

Other (OTH) AF: 0.507 AC: 1070 AN: 2112

Alfa AF: 0.493 Hom.: 44899

Bravo AF: 0.487

Asia WGS AF: 0.391 AC: 1362 AN: 3478

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	-0.81
CADD	Benign	5.1
DANN	Benign	0.55
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2235013; hg19: chr7-87178626; COSMIC: COSV55951857;