rs1810711

Positions:

• chr9-96246276-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000197.2(HSD17B3):​c.524+280A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,974 control chromosomes in the GnomAD database, including 19,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19202 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467

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]

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-96246276-T-G is Benign according to our data. Variant chr9-96246276-T-G is described in ClinVar as [Benign]. Clinvar id is 1277485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.524+280A>C		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3291+280A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.524+280A>C		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75787 AN: 151856 Hom.: 19188 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.494

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.499 AC: 75842 AN: 151974 Hom.: 19202 Cov.: 32 AF XY: 0.504 AC XY: 37451 AN XY: 74284

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.496

Alfa AF: 0.524 Hom.: 6565

Bravo AF: 0.496

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs1810711; hg19: chr9-99008558;