7-87509329-A-G
Position:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001348946.2(ABCB1):āc.3435T>Cā(p.Ile1145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,756 control chromosomes in the GnomAD database, including 196,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.57 ( 26668 hom., cov: 31)
Exomes š: 0.48 ( 169342 hom. )
Consequence
ABCB1
NM_001348946.2 synonymous
NM_001348946.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.52
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 7-87509329-A-G is Benign according to our data. Variant chr7-87509329-A-G is described in ClinVar as [Benign]. Clinvar id is 225939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87509329-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.52 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCB1 | NM_001348946.2 | c.3435T>C | p.Ile1145= | synonymous_variant | 26/28 | ENST00000622132.5 | NP_001335875.1 | |
ABCB1 | NM_001348945.2 | c.3645T>C | p.Ile1215= | synonymous_variant | 30/32 | NP_001335874.1 | ||
ABCB1 | NM_000927.5 | c.3435T>C | p.Ile1145= | synonymous_variant | 27/29 | NP_000918.2 | ||
ABCB1 | NM_001348944.2 | c.3435T>C | p.Ile1145= | synonymous_variant | 28/30 | NP_001335873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCB1 | ENST00000622132.5 | c.3435T>C | p.Ile1145= | synonymous_variant | 26/28 | 1 | NM_001348946.2 | ENSP00000478255 | P1 |
Frequencies
GnomAD3 genomes AF: 0.572 AC: 86843AN: 151852Hom.: 26611 Cov.: 31
GnomAD3 genomes
AF:
AC:
86843
AN:
151852
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.504 AC: 126736AN: 251312Hom.: 33677 AF XY: 0.491 AC XY: 66644AN XY: 135820
GnomAD3 exomes
AF:
AC:
126736
AN:
251312
Hom.:
AF XY:
AC XY:
66644
AN XY:
135820
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.475 AC: 694396AN: 1461786Hom.: 169342 Cov.: 61 AF XY: 0.472 AC XY: 342927AN XY: 727204
GnomAD4 exome
AF:
AC:
694396
AN:
1461786
Hom.:
Cov.:
61
AF XY:
AC XY:
342927
AN XY:
727204
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.572 AC: 86962AN: 151970Hom.: 26668 Cov.: 31 AF XY: 0.569 AC XY: 42247AN XY: 74274
GnomAD4 genome
AF:
AC:
86962
AN:
151970
Hom.:
Cov.:
31
AF XY:
AC XY:
42247
AN XY:
74274
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1794
AN:
3476
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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. - |
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). - |
MDR1 POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jan 26, 2007 | - - |
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 |
Non-small cell lung carcinoma Other:1
not provided, no classification provided | literature only | Database of Curated Mutations (DoCM) | Mar 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at