Genetic Variant HSD11B2:c.664+16dupC (chr16-67436149-G-GC) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000326152.6(HSD11B2):c.664+7_664+8insC variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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
ENST00000326152.6 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.349

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 -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

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

GnomAD4 exome

AF:

0.00143

AC:

2024

AN:

1413226

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

999

AN XY:

703968

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.000981

Gnomad4 ASJ exome

AF:

0.0000788

Gnomad4 EAS exome

AF:

0.00350

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00742

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.00100

AC:

151

AN:

150936

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

73722

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00293

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000482

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

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.

16-67436149-GCC-GCCC

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