rs45483293

Positions:

chr16-67436012-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000196.4(HSD11B2):c.534G>A(p.Glu178=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 586029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-67436012-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
HSD11B2	NM_000196.4 linkuse as main transcript	c.534G>A	p.Glu178=	synonymous_variant	3/5	ENST00000326152.6	NP_000187.3
HSD11B2	XM_047434048.1 linkuse as main transcript	c.222G>A	p.Glu74=	synonymous_variant	4/6		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HSD11B2	ENST00000326152.6 linkuse as main transcript	c.534G>A	p.Glu178=	synonymous_variant	3/5	1	NM_000196.4	ENSP00000316786	P1
HSD11B2	ENST00000567684.2 linkuse as main transcript	n.397G>A		non_coding_transcript_exon_variant	3/4	3
HSD11B2	ENST00000566606.1 linkuse as main transcript	c.*335G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	5		ENSP00000473429

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

GnomAD3 exomes

AF:

0.0308

AC:

7749

AN:

251448

Hom.:

161

AF XY:

0.0316

AC XY:

4288

AN XY:

135906

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 SAS exome

AF:

0.0110

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

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.0233

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0400

GnomAD4 genome

AF:

0.0285

AC:

4348

AN:

152342

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00871

Gnomad4 AMR

AF:

0.0290

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0358

Gnomad4 NFE

AF:

0.0401

Gnomad4 OTH

AF:

0.0430

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

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 30, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Apparent mineralocorticoid excess

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.2

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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