chr17-42552994-G-T

Position:

chr17-42552994-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000413.4(HSD17B1):c.61G>T(p.Val21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

HSD17B1
NM_000413.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.785

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 (HGNC:):

HSD17B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062812775).

BP6

Variant 17-42552994-G-T is Benign according to our data. Variant chr17-42552994-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3284846.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B1	NM_000413.4 linkuse as main transcript	c.61G>T	p.Val21Leu	missense_variant	1/6	ENST00000585807.6	NP_000404.2	P14061
HSD17B1	NM_001330219.3 linkuse as main transcript	c.61G>T	p.Val21Leu	missense_variant	1/6		NP_001317148.1	A0A0A0MQS7
HSD17B1	NR_144397.2 linkuse as main transcript	n.72G>T		non_coding_transcript_exon_variant	1/5
HSD17B1-AS1	NR_144402.1 linkuse as main transcript	n.1809C>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B1	ENST00000585807.6 linkuse as main transcript	c.61G>T	p.Val21Leu	missense_variant	1/6	1	NM_000413.4	ENSP00000466799.1		P14061

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251064

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000210

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000233

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

3.9

DANN

Benign

0.84

DEOGEN2

Uncertain

0.48

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.73

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.16

Sift

Benign

0.17

.;T

Sift4G

Benign

0.26

T;T

Polyphen

0.018

B;.

Vest4

0.070

MutPred

0.47

Loss of methylation at R22 (P = 0.1235);Loss of methylation at R22 (P = 0.1235);

MVP

0.79

MPC

0.31

ClinPred

0.0067

GERP RS

-0.59

Varity_R

0.14

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over