chr16-82085495-G-A

Variant names:

• chr16-82085495-G-A
• rs1364287
• NM_002153.3:c.665-5407G>A

Variant summary

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

The NM_002153.3(HSD17B2):​c.665-5407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,976 control chromosomes in the GnomAD database, including 6,611 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 (6611 hom., cov: 32)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 5 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]

HSD17B2-AS1 (HGNC:56281): (HSD17B2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.665-5407G>A		intron_variant	Intron 3 of 4	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.665-4670G>A		intron_variant	Intron 3 of 3		XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.665-5407G>A		intron_variant	Intron 3 of 4	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.257-5407G>A		intron_variant	Intron 3 of 4	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.293-5407G>A		intron_variant	Intron 2 of 2	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.2	n.44-14306C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42152 AN: 151858 Hom.: 6609 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.277 AC: 42160 AN: 151976 Hom.: 6611 Cov.: 32 AF XY: 0.277 AC XY: 20593 AN XY: 74252

African (AFR) AF: 0.160 AC: 6624 AN: 41462

American (AMR) AF: 0.236 AC: 3606 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3470

East Asian (EAS) AF: 0.0599 AC: 310 AN: 5178

South Asian (SAS) AF: 0.332 AC: 1597 AN: 4814

European-Finnish (FIN) AF: 0.384 AC: 4039 AN: 10516

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24068 AN: 67954

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.320 Hom.: 12760

Bravo AF: 0.260

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.40
PhyloP100		-2.9
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: rs1364287; hg19: chr16-82119100;