11-43829758-G-T

Variant names:

• chr11-43829758-G-T
• rs11037662
• NM_016142.3:c.502-1218G>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.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
• Publications: 8 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]

ENSG00000246250 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016142.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B12	NM_016142.3	MANE Select	c.502-1218G>T		intron	N/A	NP_057226.1	Q53GQ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B12	ENST00000278353.10	TSL:1 MANE Select	c.502-1218G>T		intron	N/A	ENSP00000278353.4	Q53GQ0-1
	HSD17B12	ENST00000865203.1		c.502-1218G>T		intron	N/A	ENSP00000535262.1
	HSD17B12	ENST00000865204.1		c.499-1218G>T		intron	N/A	ENSP00000535263.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0275 AC: 1141 AN: 41464

American (AMR) AF: 0.166 AC: 2531 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2853 AN: 5166

South Asian (SAS) AF: 0.179 AC: 861 AN: 4814

European-Finnish (FIN) AF: 0.136 AC: 1432 AN: 10544

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9506 AN: 67980

Other (OTH) AF: 0.141 AC: 298 AN: 2106

Alfa AF: 0.134 Hom.: 2413

Bravo AF: 0.128

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		1.2
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: rs11037662; hg19: chr11-43851308;