rs2257157

Variant names:

• chr9-96256160-A-G
• rs2257157
• NM_000197.2:c.202-1217T>C

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-1217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,080 control chromosomes in the GnomAD database, including 15,478 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 0.45 (15478 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 20 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)

RNU6-1160P (HGNC:48123): (RNA, U6 small nuclear 1160, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.202-1217T>C		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.2969-1217T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.202-1217T>C		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.202-1217T>C		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*1878-1217T>C		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68341 AN: 151962 Hom.: 15459 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.450 AC: 68401 AN: 152080 Hom.: 15478 Cov.: 32 AF XY: 0.450 AC XY: 33481 AN XY: 74340

African (AFR) AF: 0.481 AC: 19935 AN: 41452

American (AMR) AF: 0.418 AC: 6386 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1763 AN: 5176

South Asian (SAS) AF: 0.455 AC: 2194 AN: 4824

European-Finnish (FIN) AF: 0.500 AC: 5287 AN: 10566

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30117 AN: 67992

Other (OTH) AF: 0.425 AC: 894 AN: 2104

Alfa AF: 0.439 Hom.: 28797

Bravo AF: 0.440

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.83
PhyloP100		0.22
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: rs2257157; hg19: chr9-99018442;