chr16-67435830-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000196.4(HSD11B2):c.468C>A(p.Thr156Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 1,613,970 control chromosomes in the GnomAD database, including 3,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 873 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2377 hom. )

Consequence

HSD11B2
NM_000196.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.28

Variant links:

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]

HSD11B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 16-67435830-C-A is Benign according to our data. Variant chr16-67435830-C-A is described in ClinVar as [Benign]. Clinvar id is 586028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-67435830-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4 link	c.468C>A	p.Thr156Thr	synonymous_variant	Exon 2 of 5	ENST00000326152.6	NP_000187.3	P80365
HSD11B2	XM_047434048.1 link	c.156C>A	p.Thr52Thr	synonymous_variant	Exon 3 of 6		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD11B2	ENST00000326152.6 link	c.468C>A	p.Thr156Thr	synonymous_variant	Exon 2 of 5	1	NM_000196.4	ENSP00000316786.5	P80365
HSD11B2	ENST00000566606.1 link	n.*269C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5		ENSP00000473429.1	R4GN04
HSD11B2	ENST00000567684.2 link	n.331C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3
HSD11B2	ENST00000566606.1 link	n.*269C>A		3_prime_UTR_variant	Exon 2 of 3	5		ENSP00000473429.1	R4GN04

Frequencies

GnomAD3 genomes

AF:

0.0841

AC:

12787

AN:

152124

Hom.:

870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0712

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0413

Gnomad OTH

AF:

0.0813

GnomAD3 exomes

AF:

0.0542

AC:

13602

AN:

250788

Hom.:

596

AF XY:

0.0543

AC XY:

7365

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0363

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.00250

Gnomad SAS exome

AF:

0.0812

Gnomad FIN exome

AF:

0.0362

Gnomad NFE exome

AF:

0.0439

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0479

AC:

69959

AN:

1461728

Hom.:

2377

Cov.:

AF XY:

0.0482

AC XY:

35083

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.0380

Gnomad4 ASJ exome

AF:

0.0629

Gnomad4 EAS exome

AF:

0.00166

Gnomad4 SAS exome

AF:

0.0762

Gnomad4 FIN exome

AF:

0.0405

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.0841

AC:

12801

AN:

152242

Hom.:

873

Cov.:

AF XY:

0.0825

AC XY:

6142

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.00386

Gnomad4 SAS

AF:

0.0709

Gnomad4 FIN

AF:

0.0360

Gnomad4 NFE

AF:

0.0413

Gnomad4 OTH

AF:

0.0810

Alfa

AF:

0.0496

Hom.:

349

Bravo

AF:

0.0880

Asia WGS

AF:

0.0530

AC:

182

AN:

3478

EpiCase

AF:

0.0442

EpiControl

AF:

0.0484

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16109323) -

Aug 14, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apparent mineralocorticoid excess

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.9

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over