Variant 9-96250070-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000197.2(HSD17B3):c.454-284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,386,278 control chromosomes in the GnomAD database, including 48,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5412 hom., cov: 32)

Exomes 𝑓: 0.26 ( 42980 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

HSD17B3 (HGNC:5212): (hydroxysteroid 17-beta dehydrogenase 3) This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia. [provided by RefSeq, Jul 2008]

HSD17B3 links:

ENSG00000285269 (HGNC:):

ENSG00000285269 links:

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

HSD17B3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-96250070-C-T is Benign according to our data. Variant chr9-96250070-C-T is described in ClinVar as [Benign]. Clinvar id is 1251434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.454-284G>A	intron_variant		ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
HSD17B3-AS1	NR_146524.1 link	n.748C>T	non_coding_transcript_exon_variant	3/3
SLC35D2-HSD17B3	NR_182427.1 link	n.3221-284G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.454-284G>A		intron_variant		1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*2130-284G>A		intron_variant				ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39580

AN:

151860

Hom.:

5405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.258

AC:

318095

AN:

1234300

Hom.:

42980

Cov.:

AF XY:

0.254

AC XY:

151726

AN XY:

596298

show subpopulations

Gnomad4 AFR exome

AF:

0.312

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.0213

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.261

AC:

39621

AN:

151978

Hom.:

5412

Cov.:

AF XY:

0.255

AC XY:

18940

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.0286

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.265

Hom.:

720

Bravo

AF:

0.256

Asia WGS

AF:

0.109

AC:

378

AN:

3478

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	GeneDx	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.42

DANN

Benign

0.70

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