rs145164937
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_022436.3(ABCG5):āc.293C>Gā(p.Ala98Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,581,976 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A98C) has been classified as Uncertain significance.
Frequency
Consequence
NM_022436.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCG5 | NM_022436.3 | c.293C>G | p.Ala98Gly | missense_variant | 3/13 | ENST00000405322.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCG5 | ENST00000405322.8 | c.293C>G | p.Ala98Gly | missense_variant | 3/13 | 1 | NM_022436.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00200 AC: 304AN: 152162Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00237 AC: 463AN: 194998Hom.: 1 AF XY: 0.00254 AC XY: 267AN XY: 105104
GnomAD4 exome AF: 0.00214 AC: 3061AN: 1429696Hom.: 12 Cov.: 33 AF XY: 0.00218 AC XY: 1542AN XY: 707604
GnomAD4 genome AF: 0.00200 AC: 304AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.00208 AC XY: 155AN XY: 74458
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 25, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 10, 2017 | - - |
Sitosterolemia 1 Uncertain:1Benign:1
Uncertain significance, no assertion criteria provided | research | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | ABCG5: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2022 | See Variant Classification Assertion Criteria. - |
ABCG5-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2024 | The ABCG5 c.293C>G variant is predicted to result in the amino acid substitution p.Ala98Gly. This variant was reported in the heterozygous state in three Argentinian individuals with hypercholesterolemia (Corral et al. 2018. PubMed ID: 30270055). This variant was also identified in the heterozygous state in two unrelated patients with moderate thrombocytopenia and bleeding scores of 0 and 4 (Ali et al. 2016. PubMed ID: 27291889). A blood smear from the patient with the bleeding score of 0 revealed stomatocytes which, along with macrothrombocytopenia, are a feature of sitosterolemia, a disorder associated with recessive inheritance of variants in the ABCG5 gene. A second pathogenic variant was not identified in either patient in the Ali et al. report. This variant is reported in 1.0% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, and one homozygous individual has been documented. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Hyperuricemic nephropathy, familial juvenile type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 05, 2021 | - - |
Sitosterolemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 04, 2020 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at