17-42554661-C-T

Position:

chr17-42554661-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000585807.6(HSD17B1):c.718-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,604,372 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 11 hom., cov: 34)

Exomes 𝑓: 0.012 ( 174 hom. )

Consequence

HSD17B1
ENST00000585807.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004899

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-42554661-C-T is Benign according to our data. Variant chr17-42554661-C-T is described in ClinVar as [Benign]. Clinvar id is 771028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
HSD17B1	NM_000413.4 linkuse as main transcript	c.718-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000585807.6	NP_000404.2
HSD17B1-AS1	NR_144402.1 linkuse as main transcript	n.142G>A	non_coding_transcript_exon_variant	1/1
HSD17B1	NM_001330219.3 linkuse as main transcript	c.721-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001317148.1
HSD17B1	NR_144397.2 linkuse as main transcript	n.635-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
HSD17B1	ENST00000585807.6 linkuse as main transcript	c.718-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000413.4	ENSP00000466799	P4
HSD17B1-AS1	ENST00000590513.3 linkuse as main transcript	n.181G>A	non_coding_transcript_exon_variant	1/1
HSD17B1	ENST00000225929.5 linkuse as main transcript	c.721-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000225929	A2
HSD17B1	ENST00000590299.5 linkuse as main transcript	c.*174-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000465128

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1203

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00961

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00785

AC:

1844

AN:

235054

Hom.:

AF XY:

0.00738

AC XY:

954

AN XY:

129250

show subpopulations

Gnomad AFR exome

AF:

0.00272

Gnomad AMR exome

AF:

0.00639

Gnomad ASJ exome

AF:

0.00606

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000362

Gnomad FIN exome

AF:

0.00436

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.0121

AC:

17522

AN:

1452012

Hom.:

174

Cov.:

AF XY:

0.0116

AC XY:

8400

AN XY:

722456

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00666

Gnomad4 ASJ exome

AF:

0.00707

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000534

Gnomad4 FIN exome

AF:

0.00495

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.00939

GnomAD4 genome

AF:

0.00790

AC:

1203

AN:

152360

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

527

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.00960

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00816

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.9

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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