rs717620
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000392.5(ABCC2):c.-24C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,610,598 control chromosomes in the GnomAD database, including 29,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 2125 hom., cov: 33)
Exomes 𝑓: 0.19 ( 27698 hom. )
Consequence
ABCC2
NM_000392.5 5_prime_UTR
NM_000392.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
Genes affected
ABCC2 (HGNC:53): (ATP binding cassette subfamily C member 2) The 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 MRP subfamily which is involved in multi-drug resistance. This protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells. Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 10-99782821-C-T is Benign according to our data. Variant chr10-99782821-C-T is described in ClinVar as [Benign]. Clinvar id is 298437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCC2 | NM_000392.5 | c.-24C>T | 5_prime_UTR_variant | 1/32 | ENST00000647814.1 | NP_000383.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCC2 | ENST00000647814.1 | c.-24C>T | 5_prime_UTR_variant | 1/32 | NM_000392.5 | ENSP00000497274 | P1 |
Frequencies
GnomAD3 genomes AF: 0.155 AC: 23555AN: 152080Hom.: 2127 Cov.: 33
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GnomAD3 exomes AF: 0.171 AC: 42814AN: 251040Hom.: 3942 AF XY: 0.171 AC XY: 23245AN XY: 135676
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GnomAD4 exome AF: 0.190 AC: 276603AN: 1458400Hom.: 27698 Cov.: 31 AF XY: 0.188 AC XY: 136569AN XY: 725676
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GnomAD4 genome AF: 0.155 AC: 23547AN: 152198Hom.: 2125 Cov.: 33 AF XY: 0.156 AC XY: 11601AN XY: 74402
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ClinVar
Significance: Benign
Submissions summary: Benign:5
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 | Jun 18, 2021 | This variant is associated with the following publications: (PMID: 19415824, 22664480, 16788565, 24743544, 19890061, 21451505) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 18, 2017 | - - |
ABCC2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 22, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Dubin-Johnson syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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