11-43798974-C-T

Variant names:

• chr11-43798974-C-T
• rs1878851
• NM_016142.3:c.391+547C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016142.3(HSD17B12):​c.391+547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,946 control chromosomes in the GnomAD database, including 32,948 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 (32948 hom., cov: 31)
• Consequence: HSD17B12 NM_016142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 7 publications found

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]

ENSG00000283341 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B12	NM_016142.3	c.391+547C>T		intron_variant	Intron 4 of 10	ENST00000278353.10	NP_057226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B12	ENST00000278353.10	c.391+547C>T		intron_variant	Intron 4 of 10	1	NM_016142.3	ENSP00000278353.4

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99480 AN: 151828 Hom.: 32905 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.655 AC: 99565 AN: 151946 Hom.: 32948 Cov.: 31 AF XY: 0.656 AC XY: 48745 AN XY: 74280

African (AFR) AF: 0.599 AC: 24795 AN: 41416

American (AMR) AF: 0.561 AC: 8556 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2181 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3853 AN: 5164

South Asian (SAS) AF: 0.678 AC: 3266 AN: 4816

European-Finnish (FIN) AF: 0.683 AC: 7207 AN: 10552

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47444 AN: 67952

Other (OTH) AF: 0.662 AC: 1395 AN: 2106

Alfa AF: 0.678 Hom.: 4581

Bravo AF: 0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.78
DANN	Benign	0.73
PhyloP100		-1.0
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: rs1878851; hg19: chr11-43820524;