16-82081543-C-T

Variant names:

• chr16-82081543-C-T
• rs9889094
• NM_002153.3:c.665-9359C>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.665-9359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,140 control chromosomes in the GnomAD database, including 1,116 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 0.091 (1116 hom., cov: 32)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.665-9359C>T		intron_variant	Intron 3 of 4	ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.665-8622C>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.665-9359C>T		intron_variant	Intron 3 of 4	1	NM_002153.3	ENSP00000199936.4
HSD17B2	ENST00000568090.5	c.257-9359C>T		intron_variant	Intron 3 of 4	3		ENSP00000456529.1
HSD17B2	ENST00000566838.2	c.293-9359C>T		intron_variant	Intron 2 of 2	2		ENSP00000456471.1
HSD17B2-AS1	ENST00000567021.2	n.44-10354G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13807 AN: 152022 Hom.: 1110 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.0909 AC: 13831 AN: 152140 Hom.: 1116 Cov.: 32 AF XY: 0.0927 AC XY: 6894 AN XY: 74396

African (AFR) AF: 0.143 AC: 5920 AN: 41488

American (AMR) AF: 0.238 AC: 3640 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.166 AC: 855 AN: 5164

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0366 AC: 2490 AN: 67992

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0574 Hom.: 2209

Bravo AF: 0.109

Asia WGS AF: 0.102 AC: 354 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	5.2
DANN	Benign	0.72
PhyloP100		-0.29
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: rs9889094; hg19: chr16-82115148;