Genetic Variant ABCB1:c.*89A>T (chr7-87504154-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.417

Variant links:

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]

ABCB1 links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2 link	c.*89A>T	3_prime_UTR_variant	Exon 28 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.*89A>T	3_prime_UTR_variant	Exon 32 of 32		NP_001335874.1
ABCB1	NM_000927.5 link	c.*89A>T	3_prime_UTR_variant	Exon 29 of 29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 link	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 link	c.*89A>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_001348946.2	ENSP00000478255.1		P08183-1

Frequencies

GnomAD3 genomes

AF:

0.0871

AC:

13220

AN:

151782

Hom.:

716

Cov.:

show subpopulations

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.:

AF XY:

0.0629

AC XY:

43085

AN XY:

684472

show subpopulations

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.:

AF XY:

0.0861

AC XY:

6398

AN XY:

74292

show subpopulations

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:

AN:

3472

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over