rs439205

Positions:

• chr6-33206065-G-A
• chr6-33206065-G-C
• chr6-33206065-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014234.5(HSD17B8):​c.652-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,529,484 control chromosomes in the GnomAD database, including 56,354 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 (6797 hom., cov: 31)
  • Exomes 𝑓: 0.26 (49557 hom.)
• Consequence: HSD17B8 NM_014234.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

Genes affected

HSD17B8 (HGNC:3554): (hydroxysteroid 17-beta dehydrogenase 8) In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined. [provided by RefSeq, Jul 2008]

HSD17B8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B8	NM_014234.5	c.652-69G>A		intron_variant		ENST00000374662.4	NP_055049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B8	ENST00000374662.4	c.652-69G>A		intron_variant		1	NM_014234.5	ENSP00000363794.3
HSD17B8	ENST00000469186.1	n.816-69G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42970 AN: 151778 Hom.: 6771 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.256 AC: 352986 AN: 1377588 Hom.: 49557 Cov.: 21 AF XY: 0.256 AC XY: 176225 AN XY: 687440

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.283 AC: 43043 AN: 151896 Hom.: 6797 Cov.: 31 AF XY: 0.285 AC XY: 21171 AN XY: 74250

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.303

Alfa AF: 0.242 Hom.: 7773

Bravo AF: 0.288

Asia WGS AF: 0.390 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.71

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: rs439205; hg19: chr6-33173842; COSMIC: COSV63002628; COSMIC: COSV63002628;