rs12800235

Positions:

• chr11-43726362-A-G

Variant summary

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

The NM_016142.3(HSD17B12):​c.161-24549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,918 control chromosomes in the GnomAD database, including 8,832 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 0.34 (8832 hom., cov: 31)
• Consequence: HSD17B12 NM_016142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B12	NM_016142.3	c.161-24549A>G		intron_variant		ENST00000278353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B12	ENST00000278353.10	c.161-24549A>G		intron_variant		1	NM_016142.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51222 AN: 151800 Hom.: 8820 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.337 AC: 51247 AN: 151918 Hom.: 8832 Cov.: 31 AF XY: 0.334 AC XY: 24777 AN XY: 74246

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.350

Alfa AF: 0.336 Hom.: 4464

Bravo AF: 0.338

Asia WGS AF: 0.320 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.64

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: rs12800235; hg19: chr11-43747912;