rs45598932

chr16-67430908-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000567261.1(ENSG00000261320):n.234C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,026 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (51 hom., cov: 32)
  • Exomes 𝑓: 0.020 (1 hom.)
• Consequence: ENST00000567261.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

Genes affected

(HGNC:):

HSD11B2 (HGNC:5209): (hydroxysteroid 11-beta dehydrogenase 2) There are at least two isozymes of the corticosteroid 11-beta-dehydrogenase, a microsomal enzyme complex responsible for the interconversion of cortisol and cortisone. The type I isozyme has both 11-beta-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) activities. The type II isozyme, encoded by this gene, has only 11-beta-dehydrogenase activity. In aldosterone-selective epithelial tissues such as the kidney, the type II isozyme catalyzes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. In tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, it protects cells from the growth-inhibiting and/or pro-apoptotic effects of cortisol, particularly during embryonic development. Mutations in this gene cause the syndrome of apparent mineralocorticoid excess and hypertension. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-67430908-G-A is Benign according to our data. Variant chr16-67430908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0259 (3869/149426) while in subpopulation NFE AF= 0.031 (2081/67200). AF 95% confidence interval is 0.0299. There are 51 homozygotes in gnomad4. There are 1813 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B2	XM_047434048.1	c.-48+129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000567261.1	n.234C>T		non_coding_transcript_exon_variant	2/2	3
HSD11B2	ENST00000567684.2	n.128+129G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3863 AN: 149336 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0312

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0291

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.0390

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0300

GnomAD4 exome AF: 0.0204 AC: 53 AN: 2600 Hom.: 1 Cov.: 0 AF XY: 0.0208 AC XY: 29 AN XY: 1392

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0256

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00532

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0183

GnomAD4 genome AF: 0.0259 AC: 3869 AN: 149426 Hom.: 51 Cov.: 32 AF XY: 0.0249 AC XY: 1813 AN XY: 72858

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00851

Gnomad4 SAS AF: 0.0289

Gnomad4 FIN AF: 0.00951

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0294 Hom.: 17

Bravo AF: 0.0258

Asia WGS AF: 0.0290 AC: 99 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

This variant is associated with the following publications: (PMID: 17551100) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.8
Dann	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45598932; hg19: chr16-67464811; COSMIC: COSV58204050;