16-82071851-G-C

Position:

• chr16-82071851-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002153.3(HSD17B2):​c.664+724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 153,688 control chromosomes in the GnomAD database, including 81 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 0.028 (79 hom., cov: 33)
  • Exomes 𝑓: 0.043 (2 hom.)
• Consequence: HSD17B2 NM_002153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0284 (4332/152282) while in subpopulation NFE AF= 0.042 (2859/68012). AF 95% confidence interval is 0.0408. There are 79 homozygotes in gnomad4. There are 2033 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B2	NM_002153.3	c.664+724G>C		intron_variant		ENST00000199936.9	NP_002144.1
HSD17B2	XM_047434049.1	c.664+724G>C		intron_variant			XP_047290005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B2	ENST00000199936.9	c.664+724G>C		intron_variant		1	NM_002153.3	ENSP00000199936.4

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4335 AN: 152164 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0427 AC: 60 AN: 1406 Hom.: 2 Cov.: 0 AF XY: 0.0440 AC XY: 33 AN XY: 750

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0478

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0284 AC: 4332 AN: 152282 Hom.: 79 Cov.: 33 AF XY: 0.0273 AC XY: 2033 AN XY: 74460

Gnomad4 AFR AF: 0.00799

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0114 Hom.: 4

Bravo AF: 0.0279

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.75

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: rs8191175; hg19: chr16-82105456;