chr5-119536489-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000414.4(HSD17B4):c.2060C>T(p.Thr687Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,611,912 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts 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.2060C>T | p.Thr687Ile | missense_variant | Exon 23 of 24 | ENST00000510025.7 | NP_000405.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00365 AC: 555AN: 152082Hom.: 13 Cov.: 32
GnomAD3 exomes AF: 0.00699 AC: 1756AN: 251164Hom.: 61 AF XY: 0.00682 AC XY: 926AN XY: 135740
GnomAD4 exome AF: 0.00309 AC: 4517AN: 1459712Hom.: 167 Cov.: 30 AF XY: 0.00321 AC XY: 2332AN XY: 726222
GnomAD4 genome AF: 0.00363 AC: 553AN: 152200Hom.: 13 Cov.: 32 AF XY: 0.00429 AC XY: 319AN XY: 74426
ClinVar
Submissions by phenotype
not specified Benign:3
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. -
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). -
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. -
Bifunctional peroxisomal enzyme deficiency Benign:1
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. -
Bifunctional peroxisomal enzyme deficiency;C4551721:Perrault syndrome 1 Benign:1
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Bifunctional peroxisomal enzyme deficiency;C0685838:Perrault syndrome Benign:1
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not provided Benign:1
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Perrault syndrome 1 Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at