rs10459247

Variant names:

• chr12-56777732-T-C
• rs10459247
• NM_003725.4:c.313+3567T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003725.4(HSD17B6):​c.313+3567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,094 control chromosomes in the GnomAD database, including 3,607 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 0.21 (3607 hom., cov: 32)
• Consequence: HSD17B6 NM_003725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 9 publications found

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]

ENSG00000309589 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B6	NM_003725.4	c.313+3567T>C		intron_variant	Intron 2 of 4	ENST00000322165.1	NP_003716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B6	ENST00000322165.1	c.313+3567T>C		intron_variant	Intron 2 of 4	1	NM_003725.4	ENSP00000318631.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32078 AN: 151976 Hom.: 3601 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.211 AC: 32085 AN: 152094 Hom.: 3607 Cov.: 32 AF XY: 0.208 AC XY: 15474 AN XY: 74334

African (AFR) AF: 0.146 AC: 6054 AN: 41514

American (AMR) AF: 0.225 AC: 3438 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1414 AN: 5166

South Asian (SAS) AF: 0.204 AC: 983 AN: 4808

European-Finnish (FIN) AF: 0.172 AC: 1814 AN: 10558

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16659 AN: 67986

Other (OTH) AF: 0.230 AC: 486 AN: 2110

Alfa AF: 0.215 Hom.: 528

Bravo AF: 0.214

Asia WGS AF: 0.222 AC: 773 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.31
PhyloP100		-0.81
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: rs10459247; hg19: chr12-57171516;