rs1886260

Positions:

• chr9-96250615-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.453+803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 326,016 control chromosomes in the GnomAD database, including 12,772 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 0.28 (6448 hom., cov: 31)
  • Exomes 𝑓: 0.26 (6324 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.453+803T>C		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3220+803T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.453+803T>C		intron_variant		1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2129+803T>C		intron_variant				ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42578 AN: 151826 Hom.: 6435 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.261 AC: 45411 AN: 174072 Hom.: 6324 AF XY: 0.260 AC XY: 21500 AN XY: 82546

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.0180

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.281 AC: 42626 AN: 151944 Hom.: 6448 Cov.: 31 AF XY: 0.274 AC XY: 20320 AN XY: 74274

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.269

Alfa AF: 0.277 Hom.: 788

Bravo AF: 0.280

Asia WGS AF: 0.114 AC: 396 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	0.031
DANN	Benign	0.093

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: rs1886260; hg19: chr9-99012897;