12-56768208-A-G

Variant names:

• chr12-56768208-A-G
• rs7967600
• NM_003725.4:c.-20+4794A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 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.-20+4794A>G		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.-20+4794A>G		intron	N/A	ENSP00000318631.1
	HSD17B6	ENST00000554150.5	TSL:5	c.-20+4794A>G		intron	N/A	ENSP00000452273.1
	HSD17B6	ENST00000554643.5	TSL:5	c.-20+4794A>G		intron	N/A	ENSP00000451406.1

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

African (AFR) AF: 0.410 AC: 16976 AN: 41370

American (AMR) AF: 0.668 AC: 10170 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2021 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3771 AN: 5174

South Asian (SAS) AF: 0.741 AC: 3567 AN: 4812

European-Finnish (FIN) AF: 0.698 AC: 7345 AN: 10528

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42558 AN: 67956

Other (OTH) AF: 0.611 AC: 1289 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.77
PhyloP100		0.047
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: rs7967600; hg19: chr12-57161992;