rs17064

chr7-87504154-T-A

Variant summary

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

The NM_001348946.2(ABCB1):c.*89A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 1,528,412 control chromosomes in the GnomAD database, including 4,131 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 0.087 (717 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3414 hom.)
• Consequence: ABCB1 NM_001348946.2 3_prime_UTR
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.417

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.*89A>T		3_prime_UTR_variant	28/28	ENST00000622132.5
ABCB1	NM_000927.5	c.*89A>T		3_prime_UTR_variant	29/29
ABCB1	NM_001348944.2	c.*89A>T		3_prime_UTR_variant	30/30
ABCB1	NM_001348945.2	c.*89A>T		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.*89A>T		3_prime_UTR_variant	28/28	1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13220 AN: 151782 Hom.: 716 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0871

GnomAD4 exome AF: 0.0648 AC: 89226 AN: 1376520 Hom.: 3414 Cov.: 23 AF XY: 0.0629 AC XY: 43085 AN XY: 684472

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0431

Gnomad4 ASJ exome AF: 0.0807

Gnomad4 EAS exome AF: 0.0000533

Gnomad4 SAS exome AF: 0.00825

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.0676

Gnomad4 OTH exome AF: 0.0670

GnomAD4 genome AF: 0.0871 AC: 13227 AN: 151892 Hom.: 717 Cov.: 32 AF XY: 0.0861 AC XY: 6398 AN XY: 74292

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0643 Hom.: 188

Bravo AF: 0.0889

Asia WGS AF: 0.0160 AC: 55 AN: 3472

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	-0.80
Cadd	Benign	2.8
Dann	Benign	0.78

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: rs17064; hg19: chr7-87133470;