12-56776034-G-T

Position:

• chr12-56776034-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B6	NM_003725.4	c.313+1869G>T		intron_variant		ENST00000322165.1	NP_003716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B6	ENST00000322165.1	c.313+1869G>T		intron_variant		1	NM_003725.4	ENSP00000318631.1

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

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.397

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.56

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: rs10459246; hg19: chr12-57169818;