rs12809466

Positions:

• chr12-56773726-A-G

Variant summary

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

The ENST00000322165.1(HSD17B6):​c.-19-108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,069,036 control chromosomes in the GnomAD database, including 2,848 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 0.080 (535 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2313 hom.)
• Consequence: HSD17B6 ENST00000322165.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

Genes affected

HSD17B6 (HGNC:23316): (hydroxysteroid 17-beta dehydrogenase 6) The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B6	NM_003725.4	c.-19-108A>G		intron_variant		ENST00000322165.1	NP_003716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B6	ENST00000322165.1	c.-19-108A>G		intron_variant		1	NM_003725.4	ENSP00000318631	P1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12169 AN: 152178 Hom.: 534 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.0769

GnomAD4 exome AF: 0.0672 AC: 61650 AN: 916740 Hom.: 2313 AF XY: 0.0662 AC XY: 29947 AN XY: 452414

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0530

Gnomad4 ASJ exome AF: 0.0561

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.0322

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0799 AC: 12176 AN: 152296 Hom.: 535 Cov.: 32 AF XY: 0.0796 AC XY: 5924 AN XY: 74462

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.0779

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0757 Hom.: 90

Bravo AF: 0.0796

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
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: rs12809466; hg19: chr12-57167510;