16-82039139-C-G

Variant names:

• chr16-82039139-C-G
• rs8059915
• NM_002153.3:c.265+3450C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. 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
	HSD17B2	NM_002153.3	MANE Select	c.265+3450C>G		intron	N/A	NP_002144.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.265+3450C>G		intron	N/A	ENSP00000199936.4
	HSD17B2	ENST00000569351.2	TSL:2	c.49+3450C>G		intron	N/A	ENSP00000454931.1
	HSD17B2	ENST00000566213.1	TSL:3	c.265+3450C>G		intron	N/A	ENSP00000457943.1

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

African (AFR) AF: 0.249 AC: 10301 AN: 41332

American (AMR) AF: 0.624 AC: 9512 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1680 AN: 3464

East Asian (EAS) AF: 0.311 AC: 1598 AN: 5144

South Asian (SAS) AF: 0.525 AC: 2516 AN: 4794

European-Finnish (FIN) AF: 0.592 AC: 6209 AN: 10488

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

European-Non Finnish (NFE) AF: 0.615 AC: 41753 AN: 67890

Other (OTH) AF: 0.507 AC: 1066 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.81
DANN	Benign	0.29
PhyloP100		-0.15
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: rs8059915; hg19: chr16-82072744;