Submissions for variant NM_000414.4(HSD17B4):c.2060C>T (p.Thr687Ile)

gnomAD frequency: 0.00265  dbSNP: rs28943592

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218324	SCV000269162	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Thr712Ile in exon 24 of HSD17B4: This variant is not expected to have clinical s ignificance because it has been identified in 6.5% (13/200) of Han Chinese chrom osomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm. nih.gov/projects/SNP; dbSNP rs28943592).
Illumina Laboratory Services, Illumina	RCV000301707	SCV000452149	benign	Perrault syndrome 1	2018-01-13	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 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.
Illumina Laboratory Services, Illumina	RCV000361158	SCV000452150	benign	Bifunctional peroxisomal enzyme deficiency	2018-01-13	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 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.
GeneDx	RCV000218324	SCV000729945	benign	not specified	2017-09-20	criteria provided, single submitter	clinical testing	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000218324	SCV000917531	benign	not specified	2018-02-01	criteria provided, single submitter	clinical testing	Variant summary: HSD17B4 c.2060C>T (p.Thr687Ile) results in a non-conservative amino acid change located in the SCP2 sterol-binding domain of in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0065 in 276846 control chromosomes, predominantly at a frequency of 0.08 within the East Asian subpopulation in the gnomAD database, including 57 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 27.045 fold of the estimated maximal expected allele frequency for a pathogenic variant in HSD17B4 causing D-Bifunctional Protein Deficiency phenotype (0.003), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Multiple clinical diagnostic laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079319	SCV001113767	benign	Bifunctional peroxisomal enzyme deficiency; Perrault syndrome	2025-01-23	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000966445	SCV001144223	benign	not provided	2018-12-11	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002494555	SCV002800628	benign	Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1	2022-02-23	criteria provided, single submitter	clinical testing