rs1202168

Positions:

• chr7-87566646-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000622132.5(ABCB1):​c.530+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 850,844 control chromosomes in the GnomAD database, including 87,500 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 0.40 (12761 hom., cov: 31)
  • Exomes 𝑓: 0.45 (74739 hom.)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.141

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.530+139C>T		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5	c.530+139C>T		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.530+139C>T		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.740+139C>T		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.530+139C>T		intron_variant		1	NM_001348946.2	ENSP00000478255	P1
ABCB1	ENST00000265724.8	c.530+139C>T		intron_variant		1		ENSP00000265724	P1
ABCB1	ENST00000543898.5	c.339-405C>T		intron_variant		5		ENSP00000444095

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60239 AN: 151858 Hom.: 12773 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.455 AC: 317944 AN: 698868 Hom.: 74739 AF XY: 0.463 AC XY: 170035 AN XY: 367562

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.396 AC: 60234 AN: 151976 Hom.: 12761 Cov.: 31 AF XY: 0.403 AC XY: 29907 AN XY: 74284

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.388

Alfa AF: 0.428 Hom.: 18986

Bravo AF: 0.386

Asia WGS AF: 0.578 AC: 2005 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

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	-0.82
CADD	Benign	3.7
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1202168; hg19: chr7-87195962;