Genetic Variant HSD11B2:c.265+1019C>G (chr16-67432532-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000196.4(HSD11B2):c.265+1019C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,882 control chromosomes in the GnomAD database, including 26,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 26056 hom., cov: 30)

Exomes 𝑓: 0.39 ( 30 hom. )

Consequence

HSD11B2
NM_000196.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.957

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B2	NM_000196.4 link	c.265+1019C>G		intron_variant	Intron 1 of 4	ENST00000326152.6	NP_000187.3	P80365
HSD11B2	XM_047434048.1 link	c.-48+1753C>G		intron_variant	Intron 2 of 5		XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSD11B2	ENST00000326152.6 link	c.265+1019C>G	intron_variant	Intron 1 of 4	1	NM_000196.4	ENSP00000316786.5	P80365
HSD11B2	ENST00000566606.1 link	n.148+1019C>G	intron_variant	Intron 1 of 2	5		ENSP00000473429.1	R4GN04
HSD11B2	ENST00000567684.2 link	n.128+1753C>G	intron_variant	Intron 1 of 3	3
HSD11B2	ENST00000569303.1 link	n.28-102C>G	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82366

AN:

151428

Hom.:

25996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.393

AC:

132

AN:

336

Hom.:

AF XY:

0.344

AC XY:

AN XY:

244

show subpopulations

Gnomad4 AFR exome

AF:

1.00

AC:

AN:

Gnomad4 AMR exome

AF:

0.500

AC:

AN:

Gnomad4 ASJ exome

AF:

0.250

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

0.300

AC:

AN:

Gnomad4 NFE exome

AF:

0.379

AC:

103

AN:

272

Gnomad4 Remaining exome

AF:

0.529

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome 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

GnomAD4 genome

AF:

0.544

AC:

82484

AN:

151546

Hom.:

26056

Cov.:

AF XY:

0.543

AC XY:

40196

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.879

AC:

0.878552

AN:

0.878552

Gnomad4 AMR

AF:

0.405

AC:

0.405446

AN:

0.405446

Gnomad4 ASJ

AF:

0.489

AC:

0.488741

AN:

0.488741

Gnomad4 EAS

AF:

0.169

AC:

0.169472

AN:

0.169472

Gnomad4 SAS

AF:

0.515

AC:

0.515

AN:

0.515

Gnomad4 FIN

AF:

0.470

AC:

0.470132

AN:

0.470132

Gnomad4 NFE

AF:

0.417

AC:

0.417349

AN:

0.417349

Gnomad4 OTH

AF:

0.506

AC:

0.506179

AN:

0.506179

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.327

Hom.:

887

Bravo

AF:

0.548

Asia WGS

AF:

0.437

AC:

1525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.60

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over