11-43829758-G-T

Variant summary

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

The NM_016142.3(HSD17B12):c.502-1218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,024 control chromosomes in the GnomAD database, including 1,931 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 0.13 (1931 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: HSD17B12 NM_016142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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]

LOC107984328 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B12	NM_016142.3	c.502-1218G>T		intron_variant		ENST00000278353.10
LOC107984328	XR_001748197.3	n.2172C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B12	ENST00000278353.10	c.502-1218G>T		intron_variant		1	NM_016142.3	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19135 AN: 151904 Hom.: 1934 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.126 AC: 19130 AN: 152022 Hom.: 1931 Cov.: 32 AF XY: 0.130 AC XY: 9685 AN XY: 74276

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.141

Alfa AF: 0.131 Hom.: 1262

Bravo AF: 0.128

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	14
Dann	Benign	0.66

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: rs11037662; hg19: chr11-43851308;