rs1211152

Positions:

• chr7-87585798-A-C
• chr7-87585798-A-G
• chr7-87585798-A-T

Variant summary

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

The NM_001348946.2(ABCB1):​c.118-118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 1,007,268 control chromosomes in the GnomAD database, including 447,216 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 0.96 (69578 hom., cov: 32)
  • Exomes 𝑓: 0.94 (377638 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.54

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.118-118T>G		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.328-118T>G		intron_variant			NP_001335874.1
ABCB1	NM_000927.5	c.118-118T>G		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.118-118T>G		intron_variant			NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.118-118T>G		intron_variant		1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.118-118T>G		intron_variant		1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.118-118T>G		intron_variant		5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.118-118T>G		intron_variant		5		ENSP00000399419.1

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145374 AN: 152172 Hom.: 69514 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.961

GnomAD4 exome AF: 0.939 AC: 803069 AN: 854978 Hom.: 377638 AF XY: 0.942 AC XY: 414572 AN XY: 440244

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.982

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.992

Gnomad4 FIN exome AF: 0.916

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.952

GnomAD4 genome AF: 0.955 AC: 145497 AN: 152290 Hom.: 69578 Cov.: 32 AF XY: 0.958 AC XY: 71327 AN XY: 74464

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.961

Alfa AF: 0.942 Hom.: 67545

Bravo AF: 0.961

Asia WGS AF: 0.995 AC: 3461 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	-0.91
CADD	Benign	0.39
DANN	Benign	0.75

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: rs1211152; hg19: chr7-87215114;