Genetic Variant ENST00000488737.6:n.1549G>C (chr7-87504179-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000488737.6(ABCB1):n.1549G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ABCB1
ENST00000488737.6 non_coding_transcript_exon

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.748

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2 link	c.*64G>C	3_prime_UTR_variant	Exon 28 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.*64G>C	3_prime_UTR_variant	Exon 32 of 32		NP_001335874.1
ABCB1	NM_000927.5 link	c.*64G>C	3_prime_UTR_variant	Exon 29 of 29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 link	c.*64G>C	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 link	c.*64G>C		3_prime_UTR_variant	Exon 28 of 28	1	NM_001348946.2	ENSP00000478255.1		P08183-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1446936

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33056

American (AMR)

AF:

0.0000680

AC:

AN:

44092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39372

South Asian (SAS)

AF:

0.00

AC:

AN:

85102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5088

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101398

Other (OTH)

AF:

0.00

AC:

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

-0.76

CADD

Benign

2.8

(source)

DANN

Benign

0.76

PhyloP100

-0.75

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

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ENST00000488737.6:n.1549G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over