12-56776034-G-T

Variant names:

• chr12-56776034-G-T
• rs10459246
• NM_003725.4:c.313+1869G>T

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+1869G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,892 control chromosomes in the GnomAD database, including 15,594 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 0.43 (15594 hom., cov: 31)
• Consequence: HSD17B6 NM_003725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003725.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B6	NM_003725.4	MANE Select	c.313+1869G>T		intron	N/A	NP_003716.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B6	ENST00000322165.1	TSL:1 MANE Select	c.313+1869G>T		intron	N/A	ENSP00000318631.1
	HSD17B6	ENST00000859675.1		c.314-638G>T		intron	N/A	ENSP00000529734.1
	HSD17B6	ENST00000554150.5	TSL:5	c.313+1869G>T		intron	N/A	ENSP00000452273.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65539 AN: 151774 Hom.: 15553 Cov.: 31

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.432 AC: 65635 AN: 151892 Hom.: 15594 Cov.: 31 AF XY: 0.425 AC XY: 31535 AN XY: 74228

African (AFR) AF: 0.641 AC: 26555 AN: 41410

American (AMR) AF: 0.336 AC: 5120 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1490 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1408 AN: 5146

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4814

European-Finnish (FIN) AF: 0.299 AC: 3156 AN: 10540

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25468 AN: 67938

Other (OTH) AF: 0.397 AC: 839 AN: 2112

Alfa AF: 0.208 Hom.: 394

Bravo AF: 0.446

Asia WGS AF: 0.274 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.56
PhyloP100		-1.5
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: rs10459246; hg19: chr12-57169818;