rs74091680

Positions:

• chr12-56761038-C-A
• chr12-56761038-C-T

Variant summary

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

The ENST00000554150.5(HSD17B6):​c.-230-2166C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,052 control chromosomes in the GnomAD database, including 888 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 0.077 (888 hom., cov: 31)
• Consequence: HSD17B6 ENST00000554150.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B6	ENST00000554150.5	c.-230-2166C>A		intron_variant		5		P1
HSD17B6	ENST00000554155.1	c.-231-2160C>A		intron_variant		3
HSD17B6	ENST00000554643.5	c.-216-2180C>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11728 AN: 151934 Hom.: 881 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0773 AC: 11760 AN: 152052 Hom.: 888 Cov.: 31 AF XY: 0.0765 AC XY: 5685 AN XY: 74324

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.0525

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0142 Hom.: 3

Bravo AF: 0.0817

Asia WGS AF: 0.0360 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.65

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: rs74091680; hg19: chr12-57154822;