rs1128503
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001348946.2(ABCB1):āc.1236T>Cā(p.Gly412=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,758 control chromosomes in the GnomAD database, including 256,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.62 ( 30325 hom., cov: 32)
Exomes š: 0.55 ( 226668 hom. )
Consequence
ABCB1
NM_001348946.2 synonymous
NM_001348946.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.153
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 7-87550285-A-G is Benign according to our data. Variant chr7-87550285-A-G is described in ClinVar as [Benign]. Clinvar id is 194187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87550285-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.153 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCB1 | NM_001348946.2 | c.1236T>C | p.Gly412= | synonymous_variant | 12/28 | ENST00000622132.5 | NP_001335875.1 | |
ABCB1 | NM_001348945.2 | c.1446T>C | p.Gly482= | synonymous_variant | 16/32 | NP_001335874.1 | ||
ABCB1 | NM_000927.5 | c.1236T>C | p.Gly412= | synonymous_variant | 13/29 | NP_000918.2 | ||
ABCB1 | NM_001348944.2 | c.1236T>C | p.Gly412= | synonymous_variant | 14/30 | NP_001335873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCB1 | ENST00000622132.5 | c.1236T>C | p.Gly412= | synonymous_variant | 12/28 | 1 | NM_001348946.2 | ENSP00000478255 | P1 | |
ABCB1 | ENST00000265724.8 | c.1236T>C | p.Gly412= | synonymous_variant | 13/29 | 1 | ENSP00000265724 | P1 | ||
ABCB1 | ENST00000543898.5 | c.1044T>C | p.Gly348= | synonymous_variant | 12/28 | 5 | ENSP00000444095 |
Frequencies
GnomAD3 genomes AF: 0.619 AC: 93943AN: 151856Hom.: 30269 Cov.: 32
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GnomAD3 exomes AF: 0.537 AC: 134826AN: 251258Hom.: 37666 AF XY: 0.527 AC XY: 71570AN XY: 135790
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GnomAD4 exome AF: 0.553 AC: 807661AN: 1461784Hom.: 226668 Cov.: 68 AF XY: 0.547 AC XY: 397991AN XY: 727196
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GnomAD4 genome AF: 0.619 AC: 94069AN: 151974Hom.: 30325 Cov.: 32 AF XY: 0.612 AC XY: 45432AN XY: 74252
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ClinVar
Significance: Benign
Submissions summary: Benign:4Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 06, 2014 | - - |
ABCB1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 21, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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