rs4755731

Positions:

• chr11-43663618-A-G

Variant summary

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

The XM_024448571.2(HSD17B12):​c.-63+22584A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,052 control chromosomes in the GnomAD database, including 12,594 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 0.38 (12594 hom., cov: 32)
• Consequence: HSD17B12 XM_024448571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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]

ENSG00000283217 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B12	XM_024448571.2	c.-63+22584A>G		intron_variant			XP_024304339.1
HSD17B12	XM_024448572.2	c.-63+22584A>G		intron_variant			XP_024304340.1
HSD17B12	XM_024448573.2	c.-63+22584A>G		intron_variant			XP_024304341.1
HSD17B12	XM_047427074.1	c.-63+22584A>G		intron_variant			XP_047283030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283217	ENST00000526615.6	n.287-9373A>G		intron_variant		3
ENSG00000283341	ENST00000529261.5	n.312-9373A>G		intron_variant		3
ENSG00000283341	ENST00000532864.6	n.281+22584A>G		intron_variant		5
ENSG00000283217	ENST00000533358.2	n.223-9373A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58162 AN: 151934 Hom.: 12586 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.383 AC: 58191 AN: 152052 Hom.: 12594 Cov.: 32 AF XY: 0.391 AC XY: 29040 AN XY: 74332

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.402

Alfa AF: 0.413 Hom.: 6344

Bravo AF: 0.383

Asia WGS AF: 0.536 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4755731; hg19: chr11-43685168;