16-82081543-C-T

Variant names:

• chr16-82081543-C-T
• rs9889094
• NM_002153.3:c.665-9359C>T

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.232 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	ENST00000567021.1	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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0527 Hom.: 937

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

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: rs9889094; hg19: chr16-82115148;