NM_000196.4:c.664+16delC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000196.4(HSD11B2):c.664+16delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,578,856 control chromosomes in the GnomAD database, including 23 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

HSD11B2
NM_000196.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.349

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: 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 -16 ACMG points.

BP6

Variant 16-67436149-GC-G is Benign according to our data. Variant chr16-67436149-GC-G is described in ClinVar as Benign. ClinVar VariationId is 586030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00677 (1022/150950) while in subpopulation AFR AF = 0.0216 (889/41210). AF 95% confidence interval is 0.0204. There are 7 homozygotes in GnomAd4. There are 493 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4 link	c.664+16delC		intron_variant	Intron 3 of 4	ENST00000326152.6	NP_000187.3	P80365
HSD11B2	XM_047434048.1 link	c.352+16delC		intron_variant	Intron 4 of 5		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD11B2	ENST00000326152.6 link	c.664+8delC	splice_region_variant, intron_variant	Intron 3 of 4	1	NM_000196.4	ENSP00000316786.5	P80365
HSD11B2	ENST00000567684.2 link	n.527+8delC	splice_region_variant, intron_variant	Intron 3 of 3	3
HSD11B2	ENST00000566606.1 link	n.*473delC	downstream_gene_variant		5		ENSP00000473429.1	R4GN04

Frequencies

GnomAD3 genomes

AF:

0.00678

AC:

1023

AN:

150842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00311

Gnomad ASJ

AF:

0.00728

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000680

Gnomad OTH

AF:

0.00536

GnomAD2 exomes

AF:

0.00226

AC:

476

AN:

210458

AF XY:

0.00181

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00580

Gnomad EAS exome

AF:

0.000321

Gnomad FIN exome

AF:

0.000489

Gnomad NFE exome

AF:

0.000733

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00120

AC:

1717

AN:

1427906

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

805

AN XY:

710870

show subpopulations

African (AFR)

AF:

0.0240

AC:

785

AN:

32756

American (AMR)

AF:

0.00104

AC:

AN:

44090

Ashkenazi Jewish (ASJ)

AF:

0.00457

AC:

117

AN:

25590

East Asian (EAS)

AF:

0.000129

AC:

AN:

38632

South Asian (SAS)

AF:

0.000211

AC:

AN:

85232

European-Finnish (FIN)

AF:

0.000274

AC:

AN:

51110

Middle Eastern (MID)

AF:

0.00215

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.000539

AC:

585

AN:

1086072

Other (OTH)

AF:

0.00229

AC:

135

AN:

58840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

120

241

361

482

602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00677

AC:

1022

AN:

150950

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

493

AN XY:

73728

show subpopulations

African (AFR)

AF:

0.0216

AC:

889

AN:

41210

American (AMR)

AF:

0.00310

AC:

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.00728

AC:

AN:

3436

East Asian (EAS)

AF:

0.000391

AC:

AN:

5118

South Asian (SAS)

AF:

0.000419

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000681

AC:

AN:

67596

Other (OTH)

AF:

0.00530

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00121

Hom.:

Bravo

AF:

0.00789

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

HSD11B2-related disorder

Benign:1

Feb 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.35

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

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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