NM_000196.4:c.664+16dupC

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+16dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,564,162 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

HSD11B2
NM_000196.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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-G-GC is Benign according to our data. Variant chr16-67436149-G-GC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 723515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.001 (151/150936) while in subpopulation EAS AF = 0.00293 (15/5118). AF 95% confidence interval is 0.00181. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4 link	c.664+16dupC		intron_variant	Intron 3 of 4	ENST00000326152.6	NP_000187.3	P80365
HSD11B2	XM_047434048.1 link	c.352+16dupC		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+7_664+8insC	splice_region_variant, intron_variant	Intron 3 of 4	1	NM_000196.4	ENSP00000316786.5	P80365
HSD11B2	ENST00000567684.2 link	n.527+7_527+8insC	splice_region_variant, intron_variant	Intron 3 of 3	3
HSD11B2	ENST00000566606.1 link	n.472_473insC	downstream_gene_variant		5		ENSP00000473429.1	R4GN04

Frequencies

GnomAD3 genomes

AF:

0.000995

AC:

150

AN:

150828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00292

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000487

GnomAD2 exomes

AF:

0.00340

AC:

715

AN:

210458

AF XY:

0.00197

show subpopulations

Gnomad AFR exome

AF:

0.00607

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.00398

Gnomad FIN exome

AF:

0.00122

Gnomad NFE exome

AF:

0.00470

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00143

AC:

2024

AN:

1413226

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

999

AN XY:

703968

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

32438

American (AMR)

AF:

0.000981

AC:

AN:

43838

Ashkenazi Jewish (ASJ)

AF:

0.0000788

AC:

AN:

25370

East Asian (EAS)

AF:

0.00350

AC:

134

AN:

38324

South Asian (SAS)

AF:

0.00119

AC:

101

AN:

84868

European-Finnish (FIN)

AF:

0.00742

AC:

376

AN:

50646

Middle Eastern (MID)

AF:

0.00108

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

0.00115

AC:

1231

AN:

1073960

Other (OTH)

AF:

0.00120

AC:

AN:

58246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

109

217

326

434

543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00100

AC:

151

AN:

150936

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

73722

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

41212

American (AMR)

AF:

0.000198

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00293

AC:

AN:

5118

South Asian (SAS)

AF:

0.00126

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

67586

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.00260

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Apparent mineralocorticoid excess

Benign:1

Sep 28, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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