16-82039139-C-G

Variant summary

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

The NM_002153.3(HSD17B2):c.265+3450C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,660 control chromosomes in the GnomAD database, including 20,811 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 0.50 (20811 hom., cov: 29)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B2	NM_002153.3	c.265+3450C>G		intron_variant		ENST00000199936.9
HSD17B2	XM_047434049.1	c.265+3450C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B2	ENST00000199936.9	c.265+3450C>G		intron_variant		1	NM_002153.3	P1
HSD17B2	ENST00000563491.5	c.-144+3991C>G		intron_variant		3
HSD17B2	ENST00000566213.1	c.265+3450C>G		intron_variant		3
HSD17B2	ENST00000569351.2	c.49+3450C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75286 AN: 151542 Hom.: 20800 Cov.: 29

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.497 AC: 75314 AN: 151660 Hom.: 20811 Cov.: 29 AF XY: 0.498 AC XY: 36919 AN XY: 74078

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.507

Alfa AF: 0.540 Hom.: 2861

Bravo AF: 0.486

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.81
Dann	Benign	0.29

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: rs8059915; hg19: chr16-82072744;