rs2235020

chr7-87569949-T-Achr7-87569949-T-G

Variant summary

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

The NM_001348946.2(ABCB1):c.338+223A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,850 control chromosomes in the GnomAD database, including 12,077 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 0.38 (12077 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.161

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.338+223A>T		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.338+223A>T		intron_variant
ABCB1	NM_001348944.2	c.338+223A>T		intron_variant
ABCB1	NM_001348945.2	c.548+223A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.338+223A>T		intron_variant		1	NM_001348946.2	P1
ABCB1	ENST00000265724.8	c.338+223A>T		intron_variant		1		P1
ABCB1	ENST00000543898.5	c.338+223A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57875 AN: 151732 Hom.: 12088 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.381 AC: 57869 AN: 151850 Hom.: 12077 Cov.: 32 AF XY: 0.387 AC XY: 28723 AN XY: 74212

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.379

Alfa AF: 0.257 Hom.: 645

Bravo AF: 0.370

Asia WGS AF: 0.573 AC: 1984 AN: 3470

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	-0.81
Cadd	Benign	1.3
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2235020; hg19: chr7-87199265;