rs13237132

Variant names:

• chr7-87562353-C-G
• rs13237132
• NM_001348946.2:c.703-966G>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.703-966G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,080 control chromosomes in the GnomAD database, including 7,086 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 0.30 (7086 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.585
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.703-966G>C		intron_variant	Intron 7 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.913-966G>C		intron_variant	Intron 11 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.703-966G>C		intron_variant	Intron 8 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.703-966G>C		intron_variant	Intron 9 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.703-966G>C		intron_variant	Intron 7 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.703-966G>C		intron_variant	Intron 8 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.511-966G>C		intron_variant	Intron 7 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46151 AN: 151960 Hom.: 7082 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46169 AN: 152080 Hom.: 7086 Cov.: 32 AF XY: 0.302 AC XY: 22446 AN XY: 74350

African (AFR) AF: 0.258 AC: 10710 AN: 41470

American (AMR) AF: 0.370 AC: 5659 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4824

European-Finnish (FIN) AF: 0.288 AC: 3050 AN: 10586

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21727 AN: 67970

Other (OTH) AF: 0.335 AC: 705 AN: 2106

Alfa AF: 0.318 Hom.: 1130

Bravo AF: 0.309

Asia WGS AF: 0.241 AC: 841 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	-0.86
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		-0.58
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: rs13237132; hg19: chr7-87191669; COSMIC: COSV55964712;