rs597255
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000585807.6(HSD17B1):c.98-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,528 control chromosomes in the GnomAD database, including 254,706 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.56 ( 24483 hom., cov: 33)
Exomes 𝑓: 0.56 ( 230223 hom. )
Consequence
HSD17B1
ENST00000585807.6 intron
ENST00000585807.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0520
Genes affected
HSD17B1 (HGNC:5210): (hydroxysteroid 17-beta dehydrogenase 1) This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSD17B1 | NM_000413.4 | c.98-42C>T | intron_variant | ENST00000585807.6 | NP_000404.2 | |||
HSD17B1-AS1 | NR_144402.1 | n.1721G>A | non_coding_transcript_exon_variant | 1/1 | ||||
HSD17B1 | NM_001330219.3 | c.98-42C>T | intron_variant | NP_001317148.1 | ||||
HSD17B1 | NR_144397.2 | n.109-42C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSD17B1 | ENST00000585807.6 | c.98-42C>T | intron_variant | 1 | NM_000413.4 | ENSP00000466799 | P4 | |||
HSD17B1-AS1 | ENST00000590513.3 | n.1760G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.564 AC: 85715AN: 151938Hom.: 24461 Cov.: 33
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GnomAD3 exomes AF: 0.548 AC: 137557AN: 250924Hom.: 38427 AF XY: 0.550 AC XY: 74629AN XY: 135740
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GnomAD4 exome AF: 0.559 AC: 816305AN: 1461472Hom.: 230223 Cov.: 56 AF XY: 0.559 AC XY: 406676AN XY: 727026
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GnomAD4 genome AF: 0.564 AC: 85778AN: 152056Hom.: 24483 Cov.: 33 AF XY: 0.560 AC XY: 41631AN XY: 74316
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at