ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.622+5G>A

gnomAD frequency: 0.00006  dbSNP: rs536487449
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000841012 SCV000982968 likely benign not provided 2019-05-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001157567 SCV001319155 uncertain significance Perrault syndrome 1 2018-01-12 criteria provided, single submitter clinical testing 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.
Illumina Laboratory Services, Illumina RCV001157568 SCV001319156 uncertain significance Bifunctional peroxisomal enzyme deficiency 2018-01-12 criteria provided, single submitter clinical testing 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002536126 SCV003448484 uncertain significance Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2022-06-20 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the HSD17B4 gene. It does not directly change the encoded amino acid sequence of the HSD17B4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs536487449, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with HSD17B4-related conditions. ClinVar contains an entry for this variant (Variation ID: 681160). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV004538156 SCV004115165 uncertain significance HSD17B4-related disorder 2023-08-07 criteria provided, single submitter clinical testing The HSD17B4 c.622+5G>A variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-118814721-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001157568 SCV001457291 uncertain significance Bifunctional peroxisomal enzyme deficiency 2019-11-11 no assertion criteria provided clinical testing

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