dbSNP rs676387: HSD17B1:c.540-150C>A (chr17-42554255-C-A) – ACMG Classification: Benign (-12 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Variant links:

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 links:

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

HSD17B1-AS1 links:

ENSG00000266929 (HGNC:):

ENSG00000266929 links:

Genome browser will be placed here

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	Effect	Exon rank	MANE	Protein	UniProt
HSD17B1	NM_000413.4 link	c.540-150C>A	intron_variant	Intron 4 of 5	ENST00000585807.6	NP_000404.2	P14061
HSD17B1	NM_001330219.3 link	c.540-147C>A	intron_variant	Intron 4 of 5		NP_001317148.1	A0A0A0MQS7
HSD17B1-AS1	NR_144402.1 link	n.548G>T	non_coding_transcript_exon_variant	Exon 1 of 1
HSD17B1	NR_144397.2 link	n.457-150C>A	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B1	ENST00000585807.6 link	c.540-150C>A		intron_variant	Intron 4 of 5	1	NM_000413.4	ENSP00000466799.1		P14061

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38501

AN:

152088

Hom.:

5205

Cov.:

show subpopulations

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.:

AF XY:

0.294

AC XY:

140834

AN XY:

478288

show subpopulations

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.:

AF XY:

0.255

AC XY:

18984

AN XY:

74424

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over