rs9939740

Positions:

• chr16-82088376-G-A
• chr16-82088376-G-T

Variant summary

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

The NM_002153.3(HSD17B2):​c.665-2526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,940 control chromosomes in the GnomAD database, including 24,812 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 0.57 (24812 hom., cov: 32)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

HSD17B2 (HGNC:5211): (hydroxysteroid 17-beta dehydrogenase 2) Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in response to retinoic acid. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.665-2526G>A		intron_variant		ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.665-1789G>A		intron_variant			XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.665-2526G>A		intron_variant		1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.257-2526G>A		intron_variant		3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.293-2526G>A		intron_variant		2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.1	n.44-17187C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86444 AN: 151820 Hom.: 24802 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.569 AC: 86477 AN: 151940 Hom.: 24812 Cov.: 32 AF XY: 0.564 AC XY: 41843 AN XY: 74228

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.584

Alfa AF: 0.593 Hom.: 24413

Bravo AF: 0.565

Asia WGS AF: 0.464 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.77

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: rs9939740; hg19: chr16-82121981; COSMIC: COSV52276005;