16-67431372-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000196.4(HSD11B2):c.124G>A(p.Ala42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,253,710 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

HSD11B2
NM_000196.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.753

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011157364).

BP6

Variant 16-67431372-G-A is Benign according to our data. Variant chr16-67431372-G-A is described in ClinVar as [Benign]. Clinvar id is 1989648.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B2	NM_000196.4 linkuse as main transcript	c.124G>A	p.Ala42Thr	missense_variant	1/5	ENST00000326152.6
HSD11B2	XM_047434048.1 linkuse as main transcript	c.-48+593G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B2	ENST00000326152.6 linkuse as main transcript	c.124G>A	p.Ala42Thr	missense_variant	1/5	1	NM_000196.4	P1
	ENST00000567261.1 linkuse as main transcript	n.93C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

149604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000332

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000958

AC:

AN:

43840

Hom.:

AF XY:

0.000999

AC XY:

AN XY:

26034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00925

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000730

GnomAD4 exome

AF:

0.000268

AC:

296

AN:

1103998

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

153

AN XY:

536820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000254

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000714

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000414

AC:

AN:

149712

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

AN XY:

73080

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000332

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000472

ExAC

AF:

0.00150

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.21

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.70

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.50

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.38

Sift

Benign

0.061

Sift4G

Benign

0.44

Polyphen

0.80

Vest4

0.34

MutPred

0.35

Loss of stability (P = 0.1585);

MVP

0.88

MPC

1.4

ClinPred

0.082

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.32

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

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