chr12-56761038-C-A

Variant names:

• chr12-56761038-C-A
• rs74091680
• ENST00000554150.5:c.-230-2166C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.96).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B6	ENST00000554150.5	c.-230-2166C>A		intron_variant	Intron 1 of 5	5		ENSP00000452273.1
HSD17B6	ENST00000554643.5	c.-216-2180C>A		intron_variant	Intron 1 of 5	5		ENSP00000451406.1
HSD17B6	ENST00000555159.5	c.-20+8720C>A		intron_variant	Intron 1 of 4	5		ENSP00000450698.1

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

African (AFR) AF: 0.193 AC: 8013 AN: 41436

American (AMR) AF: 0.0455 AC: 694 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.00831 AC: 43 AN: 5176

South Asian (SAS) AF: 0.0525 AC: 253 AN: 4818

European-Finnish (FIN) AF: 0.0469 AC: 496 AN: 10576

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1947 AN: 68002

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0328 Hom.: 184

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
PhyloP100		-0.28
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: rs74091680; hg19: chr12-57154822;