rs723012

Variant names:

• chr16-82085167-C-T
• rs723012
• NM_002153.3:c.665-5735C>T

Variant summary

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

The NM_002153.3(HSD17B2):​c.665-5735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,108 control chromosomes in the GnomAD database, including 6,328 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 0.26 (6328 hom., cov: 33)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.827
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.665-5735C>T		intron_variant	Intron 3 of 4	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.665-4998C>T		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.665-5735C>T		intron_variant	Intron 3 of 4	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.257-5735C>T		intron_variant	Intron 3 of 4	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.293-5735C>T		intron_variant	Intron 2 of 2	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.2	n.44-13978G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39225 AN: 151990 Hom.: 6327 Cov.: 33

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.258 AC: 39225 AN: 152108 Hom.: 6328 Cov.: 33 AF XY: 0.258 AC XY: 19200 AN XY: 74348

African (AFR) AF: 0.0829 AC: 3440 AN: 41506

American (AMR) AF: 0.232 AC: 3545 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3472

East Asian (EAS) AF: 0.0607 AC: 314 AN: 5176

South Asian (SAS) AF: 0.335 AC: 1609 AN: 4810

European-Finnish (FIN) AF: 0.383 AC: 4052 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24313 AN: 67970

Other (OTH) AF: 0.268 AC: 565 AN: 2110

Alfa AF: 0.251 Hom.: 3002

Bravo AF: 0.237

Asia WGS AF: 0.205 AC: 715 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.43
PhyloP100		0.83
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: rs723012; hg19: chr16-82118772;