chr2-43812764-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_022436.3(ABCG5):c.*352T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 248,372 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
ABCG5
NM_022436.3 3_prime_UTR
NM_022436.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.174
Genes affected
ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) 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 White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCG5 | NM_022436.3 | c.*352T>C | 3_prime_UTR_variant | 13/13 | ENST00000405322.8 | NP_071881.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCG5 | ENST00000405322.8 | c.*352T>C | 3_prime_UTR_variant | 13/13 | 1 | NM_022436.3 | ENSP00000384513 | P1 | ||
ABCG5 | ENST00000486512.5 | n.2829T>C | non_coding_transcript_exon_variant | 9/9 | 1 | |||||
ABCG5 | ENST00000644754.1 | n.2692T>C | non_coding_transcript_exon_variant | 10/10 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152172Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000187 AC: 18AN: 96082Hom.: 1 Cov.: 0 AF XY: 0.000321 AC XY: 16AN XY: 49780
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Sitosterolemia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at