rs597255

chr17-42553082-C-T

Variant summary

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

The NM_000413.4(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 NM_000413.4 intron
• 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]

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=-0.89).
• 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	UniProt
HSD17B1	NM_000413.4	c.98-42C>T		intron_variant		ENST00000585807.6
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
HSD17B1	NR_144397.2	n.109-42C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B1	ENST00000585807.6	c.98-42C>T		intron_variant		1	NM_000413.4	P4
HSD17B1-AS1	ENST00000590513.3	n.1760G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85715 AN: 151938 Hom.: 24461 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.548 AC: 137557 AN: 250924 Hom.: 38427 AF XY: 0.550 AC XY: 74629 AN XY: 135740

Gnomad AFR exome AF: 0.648

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.437

Gnomad SAS exome AF: 0.636

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.508

GnomAD4 exome AF: 0.559 AC: 816305 AN: 1461472 Hom.: 230223 Cov.: 56 AF XY: 0.559 AC XY: 406676 AN XY: 727026

Gnomad4 AFR exome AF: 0.644

Gnomad4 AMR exome AF: 0.535

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.633

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.564 AC: 85778 AN: 152056 Hom.: 24483 Cov.: 33 AF XY: 0.560 AC XY: 41631 AN XY: 74316

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.516

Alfa AF: 0.534 Hom.: 4710

Bravo AF: 0.562

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.43
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs597255; hg19: chr17-40705100; COSMIC: COSV56797842; COSMIC: COSV56797842;