rs676387
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000413.4(HSD17B1):c.540-150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,118,692 control chromosomes in the GnomAD database, including 48,094 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 0.25 ( 5213 hom., cov: 34)
Exomes 𝑓: 0.29 ( 42881 hom. )
Consequence
HSD17B1
NM_000413.4 intron
NM_000413.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.23
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=-0.86).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD17B1 | NM_000413.4 | c.540-150C>A | intron_variant | ENST00000585807.6 | |||
HSD17B1-AS1 | NR_144402.1 | n.548G>T | non_coding_transcript_exon_variant | 1/1 | |||
HSD17B1 | NM_001330219.3 | c.540-147C>A | intron_variant | ||||
HSD17B1 | NR_144397.2 | n.457-150C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD17B1 | ENST00000585807.6 | c.540-150C>A | intron_variant | 1 | NM_000413.4 | P4 | |||
HSD17B1-AS1 | ENST00000590513.3 | n.587G>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.253 AC: 38501AN: 152088Hom.: 5205 Cov.: 34
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GnomAD4 exome AF: 0.290 AC: 280411AN: 966486Hom.: 42881 Cov.: 13 AF XY: 0.294 AC XY: 140834AN XY: 478288
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GnomAD4 genome ? AF: 0.253 AC: 38528AN: 152206Hom.: 5213 Cov.: 34 AF XY: 0.255 AC XY: 18984AN XY: 74424
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at