7-87549827-A-G

Variant names:

• chr7-87549827-A-G
• rs2235033
• NM_001348946.2:c.1554+24T>C

Variant summary

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

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
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.45
• Publications: 43 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=-0.8).
• 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.1554+24T>C		intron_variant	Intron 13 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.1764+24T>C		intron_variant	Intron 17 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.1554+24T>C		intron_variant	Intron 14 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.1554+24T>C		intron_variant	Intron 15 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.1554+24T>C		intron_variant	Intron 13 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.1554+24T>C		intron_variant	Intron 14 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.1362+24T>C		intron_variant	Intron 13 of 27	5		ENSP00000444095.1
ABCB1	ENST00000482527.1	n.308+24T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72601 AN: 151920 Hom.: 17424 Cov.: 32

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

GnomAD2 exomes AF: 0.460 AC: 115567 AN: 251234 AF XY: 0.456

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 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.: 37 AF XY: 0.474 AC XY: 344757 AN XY: 726786

African (AFR) AF: 0.481 AC: 16089 AN: 33460

American (AMR) AF: 0.472 AC: 21124 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14802 AN: 26132

East Asian (EAS) AF: 0.378 AC: 14990 AN: 39698

South Asian (SAS) AF: 0.379 AC: 32692 AN: 86236

European-Finnish (FIN) AF: 0.389 AC: 20743 AN: 53328

Middle Eastern (MID) AF: 0.464 AC: 2676 AN: 5768

European-Non Finnish (NFE) AF: 0.491 AC: 545157 AN: 1111140

Other (OTH) AF: 0.472 AC: 28469 AN: 60370

GnomAD4 genome AF: 0.478 AC: 72665 AN: 152038 Hom.: 17444 Cov.: 32 AF XY: 0.473 AC XY: 35166 AN XY: 74328

African (AFR) AF: 0.484 AC: 20085 AN: 41470

American (AMR) AF: 0.506 AC: 7740 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5168

South Asian (SAS) AF: 0.386 AC: 1862 AN: 4820

European-Finnish (FIN) AF: 0.380 AC: 4013 AN: 10560

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

European-Non Finnish (NFE) AF: 0.491 AC: 33379 AN: 67950

Other (OTH) AF: 0.506 AC: 1068 AN: 2110

Alfa AF: 0.492 Hom.: 84747

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

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	-0.80
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		-1.5
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: rs2235033; hg19: chr7-87179143; COSMIC: COSV55947493;