rs1810711

Variant names:

• chr9-96246276-T-G
• rs1810711
• NM_000197.2:c.524+280A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000285269 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.524+280A>C		intron_variant	Intron 7 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3291+280A>C		intron_variant	Intron 22 of 25
HSD17B3-AS1	NR_146524.1	n.-187T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.524+280A>C		intron_variant	Intron 7 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2200+280A>C		intron_variant	Intron 18 of 21			ENSP00000494818.1

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

African (AFR) AF: 0.419 AC: 17377 AN: 41432

American (AMR) AF: 0.579 AC: 8847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1463 AN: 3460

East Asian (EAS) AF: 0.582 AC: 3005 AN: 5164

South Asian (SAS) AF: 0.540 AC: 2596 AN: 4810

European-Finnish (FIN) AF: 0.546 AC: 5766 AN: 10566

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35149 AN: 67954

Other (OTH) AF: 0.496 AC: 1046 AN: 2108

Alfa AF: 0.520 Hom.: 8144

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

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1810711; hg19: chr9-99008558;