rs676387

chr17-42554255-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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]

HSD17B1-AS1 (HGNC:55314): (HSD17B1 antisense RNA 1)

ACMG classification

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: 38501 AN: 152088 Hom.: 5205 Cov.: 34

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.290 AC: 280411 AN: 966486 Hom.: 42881 Cov.: 13 AF XY: 0.294 AC XY: 140834 AN XY: 478288

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.253 AC: 38528 AN: 152206 Hom.: 5213 Cov.: 34 AF XY: 0.255 AC XY: 18984 AN XY: 74424

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.271

Alfa AF: 0.250 Hom.: 992

Bravo AF: 0.245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.9
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs676387; hg19: chr17-40706273;