rs776852403

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_000196.4(HSD11B2):c.42C>G(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,266,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L14L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

HSD11B2
NM_000196.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.97

Publications

0 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

HSD11B2 links:

ENSG00000261320 (HGNC:):

ENSG00000261320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 16-67431290-C-G is Benign according to our data. Variant chr16-67431290-C-G is described in ClinVar as Benign. ClinVar VariationId is 2967700.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.97 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000664 (10/150588) while in subpopulation EAS AF = 0.00194 (10/5156). AF 95% confidence interval is 0.00105. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000196.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B2	NM_000196.4	MANE Select	c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 5	NP_000187.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD11B2	ENST00000326152.6	TSL:1 MANE Select	c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 5	ENSP00000316786.5	P80365
HSD11B2	ENST00000855497.1		c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 5	ENSP00000525556.1
HSD11B2	ENST00000855496.1		c.42C>G	p.Leu14Leu	synonymous	Exon 1 of 5	ENSP00000525555.1

Frequencies

GnomAD3 genomes

AF:

0.0000665

AC:

AN:

150480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000361

AC:

AN:

55442

AF XY:

0.0000308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00215

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1116200

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

542528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22586

American (AMR)

AF:

0.00

AC:

AN:

18286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16444

East Asian (EAS)

AF:

0.000637

AC:

AN:

20420

South Asian (SAS)

AF:

0.0000237

AC:

AN:

42214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2990

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

928684

Other (OTH)

AF:

0.0000468

AC:

AN:

42726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000664

AC:

AN:

150588

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

73560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00194

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67366

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000982

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.4

(source)

DANN

Benign

0.80

PhyloP100

-2.0

PromoterAI

0.042

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over