rs45483293

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000196.4(HSD11B2):c.534G>A(p.Glu178Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0367 in 1,614,214 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 76 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1196 hom. )

Consequence

HSD11B2
NM_000196.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.44

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

apparent mineralocorticoid excess
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

HSD11B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 16-67436012-G-A is Benign according to our data. Variant chr16-67436012-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 586029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4 link	c.534G>A	p.Glu178Glu	synonymous_variant	Exon 3 of 5	ENST00000326152.6	NP_000187.3	P80365
HSD11B2	XM_047434048.1 link	c.222G>A	p.Glu74Glu	synonymous_variant	Exon 4 of 6		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD11B2	ENST00000326152.6 link	c.534G>A	p.Glu178Glu	synonymous_variant	Exon 3 of 5	1	NM_000196.4	ENSP00000316786.5	P80365
HSD11B2	ENST00000566606.1 link	n.*335G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5		ENSP00000473429.1	R4GN04
HSD11B2	ENST00000567684.2 link	n.397G>A		non_coding_transcript_exon_variant	Exon 3 of 4	3
HSD11B2	ENST00000566606.1 link	n.*335G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000473429.1	R4GN04

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4352

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00871

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0358

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0401

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0308

AC:

7749

AN:

251448

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0601

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0362

Gnomad NFE exome

AF:

0.0426

Gnomad OTH exome

AF:

0.0406

GnomAD4 exome

AF:

0.0375

AC:

54814

AN:

1461872

Hom.:

1196

Cov.:

AF XY:

0.0369

AC XY:

26831

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00914

AC:

306

AN:

33480

American (AMR)

AF:

0.0233

AC:

1041

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0618

AC:

1615

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0115

AC:

990

AN:

86258

European-Finnish (FIN)

AF:

0.0406

AC:

2166

AN:

53410

Middle Eastern (MID)

AF:

0.0933

AC:

538

AN:

5768

European-Non Finnish (NFE)

AF:

0.0411

AC:

45739

AN:

1112000

Other (OTH)

AF:

0.0400

AC:

2417

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

3686

7372

11059

14745

18431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1704

3408

5112

6816

8520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0285

AC:

4348

AN:

152342

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00871

AC:

362

AN:

41584

American (AMR)

AF:

0.0290

AC:

444

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

198

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.00932

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0358

AC:

381

AN:

10628

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2731

AN:

68022

Other (OTH)

AF:

0.0430

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

221

443

664

886

1107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0375

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0423

EpiControl

AF:

0.0461

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 30, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 31, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.63

CADD

Benign

7.2

(source)

DANN

Benign

0.79

PhyloP100

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over