12-56768208-A-G

Position:

• chr12-56768208-A-G

Variant summary

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

The NM_003725.4(HSD17B6):​c.-20+4794A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,848 control chromosomes in the GnomAD database, including 26,849 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 0.58 (26849 hom., cov: 29)
• Consequence: HSD17B6 NM_003725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B6	NM_003725.4	c.-20+4794A>G		intron_variant		ENST00000322165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B6	ENST00000322165.1	c.-20+4794A>G		intron_variant		1	NM_003725.4	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88528 AN: 151730 Hom.: 26846 Cov.: 29

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.583 AC: 88555 AN: 151848 Hom.: 26849 Cov.: 29 AF XY: 0.590 AC XY: 43776 AN XY: 74222

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.611

Alfa AF: 0.600 Hom.: 4124

Bravo AF: 0.572

Asia WGS AF: 0.731 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.77

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: rs7967600; hg19: chr12-57161992;