rs2888599
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_001348946.2(ABCB1):c.68+408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 152,234 control chromosomes in the GnomAD database, including 64 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 0.030 ( 64 hom., cov: 32)
Consequence
ABCB1
NM_001348946.2 intron
NM_001348946.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.72
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.03 (4565/152234) while in subpopulation NFE AF= 0.0397 (2699/68024). AF 95% confidence interval is 0.0384. There are 64 homozygotes in gnomad4. There are 2181 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd4 at 4565 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB1 | NM_001348946.2 | c.68+408G>A | intron_variant | ENST00000622132.5 | |||
ABCB1 | NM_000927.5 | c.68+408G>A | intron_variant | ||||
ABCB1 | NM_001348944.2 | c.68+408G>A | intron_variant | ||||
ABCB1 | NM_001348945.2 | c.278+408G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB1 | ENST00000622132.5 | c.68+408G>A | intron_variant | 1 | NM_001348946.2 | P1 | |||
ABCB1 | ENST00000265724.8 | c.68+408G>A | intron_variant | 1 | P1 | ||||
ABCB1 | ENST00000416177.1 | c.68+408G>A | intron_variant | 5 | |||||
ABCB1 | ENST00000543898.5 | c.68+408G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0300 AC: 4558AN: 152116Hom.: 63 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4558
AN:
152116
Hom.:
Cov.:
32
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:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0300 AC: 4565AN: 152234Hom.: 64 Cov.: 32 AF XY: 0.0293 AC XY: 2181AN XY: 74420
GnomAD4 genome
?
AF:
AC:
4565
AN:
152234
Hom.:
Cov.:
32
AF XY:
AC XY:
2181
AN XY:
74420
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:
73
AN:
3478
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
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