rs4755741

chr11-43781704-G-Achr11-43781704-G-C

Variant summary

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

The NM_016142.3(HSD17B12):c.284-16616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,910 control chromosomes in the GnomAD database, including 33,053 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 0.66 (33053 hom., cov: 31)
• Consequence: HSD17B12 NM_016142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

HSD17B12 (HGNC:18646): (hydroxysteroid 17-beta dehydrogenase 12) This gene encodes a very important 17beta-hydroxysteroid dehydrogenase (17beta-HSD) that converts estrone into estradiol in ovarian tissue. This enzyme is also involved in fatty acid elongation. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B12	NM_016142.3	c.284-16616G>A		intron_variant		ENST00000278353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B12	ENST00000278353.10	c.284-16616G>A		intron_variant		1	NM_016142.3	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99642 AN: 151794 Hom.: 33008 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.657 AC: 99729 AN: 151910 Hom.: 33053 Cov.: 31 AF XY: 0.657 AC XY: 48778 AN XY: 74236

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.660

Alfa AF: 0.686 Hom.: 30095

Bravo AF: 0.643

Asia WGS AF: 0.694 AC: 2399 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.25
Dann	Benign	0.48

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: rs4755741; hg19: chr11-43803254;