7-87504154-T-A

Variant names:

• chr7-87504154-T-A
• rs17064
• ENST00000488737.6:n.1574A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-0.8).
• 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 rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.*89A>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.*89A>T		3_prime_UTR_variant	Exon 32 of 32		NP_001335874.1
ABCB1	NM_000927.5	c.*89A>T		3_prime_UTR_variant	Exon 29 of 29		NP_000918.2
ABCB1	NM_001348944.2	c.*89A>T		3_prime_UTR_variant	Exon 30 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.*89A>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_001348946.2	ENSP00000478255.1

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

African (AFR) AF: 0.158 AC: 4958 AN: 31372

American (AMR) AF: 0.0431 AC: 1716 AN: 39784

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 2040 AN: 25286

East Asian (EAS) AF: 0.0000533 AC: 2 AN: 37550

South Asian (SAS) AF: 0.00825 AC: 667 AN: 80850

European-Finnish (FIN) AF: 0.0908 AC: 4626 AN: 50920

Middle Eastern (MID) AF: 0.100 AC: 449 AN: 4480

European-Non Finnish (NFE) AF: 0.0676 AC: 70926 AN: 1048966

Other (OTH) AF: 0.0670 AC: 3842 AN: 57312

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

African (AFR) AF: 0.149 AC: 6127 AN: 41156

American (AMR) AF: 0.0649 AC: 992 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00600 AC: 29 AN: 4834

European-Finnish (FIN) AF: 0.0953 AC: 1012 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4518 AN: 68022

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

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

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	-0.80
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		-0.42
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: rs17064; hg19: chr7-87133470;