rs2235035
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001348946.2(ABCB1):c.1554+81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,494,278 control chromosomes in the GnomAD database, including 74,142 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 0.30 ( 6809 hom., cov: 32)
Exomes 𝑓: 0.31 ( 67333 hom. )
Consequence
ABCB1
NM_001348946.2 intron
NM_001348946.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0720
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]
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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=-0.85).
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB1 | NM_001348946.2 | c.1554+81C>T | intron_variant | ENST00000622132.5 | |||
ABCB1 | NM_000927.5 | c.1554+81C>T | intron_variant | ||||
ABCB1 | NM_001348944.2 | c.1554+81C>T | intron_variant | ||||
ABCB1 | NM_001348945.2 | c.1764+81C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB1 | ENST00000622132.5 | c.1554+81C>T | intron_variant | 1 | NM_001348946.2 | P1 | |||
ABCB1 | ENST00000265724.8 | c.1554+81C>T | intron_variant | 1 | P1 | ||||
ABCB1 | ENST00000543898.5 | c.1362+81C>T | intron_variant | 5 | |||||
ABCB1 | ENST00000482527.1 | n.308+81C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.295 AC: 44893AN: 151970Hom.: 6805 Cov.: 32
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GnomAD4 exome AF: 0.313 AC: 419896AN: 1342190Hom.: 67333 AF XY: 0.310 AC XY: 209286AN XY: 674650
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GnomAD4 genome ? AF: 0.295 AC: 44917AN: 152088Hom.: 6809 Cov.: 32 AF XY: 0.295 AC XY: 21928AN XY: 74334
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ClinVar
Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at