5-119526018-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000414.4(HSD17B4):c.1675A>G(p.Ile559Val) variant causes a missense change. The variant allele was found at a frequency of 0.402 in 1,540,756 control chromosomes in the GnomAD database, including 126,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000414.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSD17B4 | NM_000414.4 | c.1675A>G | p.Ile559Val | missense_variant | Exon 19 of 24 | ENST00000510025.7 | NP_000405.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.408 AC: 61907AN: 151660Hom.: 12803 Cov.: 32
GnomAD3 exomes AF: 0.418 AC: 105063AN: 251098Hom.: 22882 AF XY: 0.405 AC XY: 54997AN XY: 135716
GnomAD4 exome AF: 0.402 AC: 557757AN: 1388978Hom.: 113963 Cov.: 24 AF XY: 0.397 AC XY: 276028AN XY: 695156
GnomAD4 genome AF: 0.408 AC: 61948AN: 151778Hom.: 12811 Cov.: 32 AF XY: 0.411 AC XY: 30483AN XY: 74152
ClinVar
Submissions by phenotype
Bifunctional peroxisomal enzyme deficiency Benign:4
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. -
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not specified Benign:4
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Ile584Val in exon 20 of HSD17B4: This variant is not expected to have clinical s ignificance because it has been identified in 40.9% (3518/8600) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs11205). -
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. -
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not provided Benign:2
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Perrault syndrome 1 Benign:2
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. -
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Bifunctional peroxisomal enzyme deficiency;C0685838:Perrault syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at