rs2476923

Variant names:

• chr9-96259379-A-G
• rs2476923
• NM_000197.2:c.202-4436T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-96259379-A-G
• chr9-96259379-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.202-4436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,048 control chromosomes in the GnomAD database, including 29,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29414 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 4 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]

HSD17B3 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000285269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-4436T>C		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-4436T>C		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-4436T>C		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1878-4436T>C		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92391 AN: 151930 Hom.: 29367 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.608 AC: 92496 AN: 152048 Hom.: 29414 Cov.: 32 AF XY: 0.599 AC XY: 44509 AN XY: 74310

African (AFR) AF: 0.796 AC: 33036 AN: 41478

American (AMR) AF: 0.574 AC: 8783 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2086 AN: 5146

South Asian (SAS) AF: 0.378 AC: 1822 AN: 4814

European-Finnish (FIN) AF: 0.499 AC: 5267 AN: 10558

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37458 AN: 67976

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.567 Hom.: 53980

Bravo AF: 0.626

Asia WGS AF: 0.414 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.35
PhyloP100		-0.0060
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: rs2476923; hg19: chr9-99021661;