16-67436149-GCC-GC

Variant names:

• chr16-67436149-GC-G
• rs72650121
• NM_000196.4:c.664+16delC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000326152.6(HSD11B2):​c.664+8delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,578,856 control chromosomes in the GnomAD database, including 23 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (16 hom.)
• Consequence: HSD11B2 ENST00000326152.6 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.349

Genes affected

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 -16 ACMG points.

• BP6: Variant 16-67436149-GC-G is Benign according to our data. Variant chr16-67436149-GC-G is described in ClinVar as [Benign]. Clinvar id is 586030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00677 (1022/150950) while in subpopulation AFR AF= 0.0216 (889/41210). AF 95% confidence interval is 0.0204. There are 7 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4	c.664+16delC		intron_variant	Intron 3 of 4	ENST00000326152.6	NP_000187.3
HSD11B2	XM_047434048.1	c.352+16delC		intron_variant	Intron 4 of 5		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B2	ENST00000326152.6	c.664+8delC		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_000196.4	ENSP00000316786.5
HSD11B2	ENST00000567684.2	n.527+8delC		splice_region_variant, intron_variant	Intron 3 of 3	3
HSD11B2	ENST00000566606.1	n.*473delC		downstream_gene_variant		5		ENSP00000473429.1

Frequencies

GnomAD3 genomes AF: 0.00678 AC: 1023 AN: 150842 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00311

Gnomad ASJ AF: 0.00728

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000680

Gnomad OTH AF: 0.00536

GnomAD3 exomes AF: 0.00226 AC: 476 AN: 210458 Hom.: 1 AF XY: 0.00181 AC XY: 209 AN XY: 115348

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00580

Gnomad EAS exome AF: 0.000321

Gnomad SAS exome AF: 0.000221

Gnomad FIN exome AF: 0.000489

Gnomad NFE exome AF: 0.000733

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.00120 AC: 1717 AN: 1427906 Hom.: 16 Cov.: 36 AF XY: 0.00113 AC XY: 805 AN XY: 710870

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00457

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.000211

Gnomad4 FIN exome AF: 0.000274

Gnomad4 NFE exome AF: 0.000539

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.00677 AC: 1022 AN: 150950 Hom.: 7 Cov.: 31 AF XY: 0.00669 AC XY: 493 AN XY: 73728

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00310

Gnomad4 ASJ AF: 0.00728

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000681

Gnomad4 OTH AF: 0.00530

Alfa AF: 0.00121 Hom.: 0

Bravo AF: 0.00789

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

HSD11B2-related disorder Benign:1

Feb 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs72650121; hg19: chr16-67470052;