16-67432532-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HSD11B2	NM_000196.4	c.265+1019C>G		intron_variant		ENST00000326152.6
HSD11B2	XM_047434048.1	c.-48+1753C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B2	ENST00000326152.6	c.265+1019C>G		intron_variant		1	NM_000196.4	P1
HSD11B2	ENST00000566606.1	c.148+1019C>G		intron_variant, NMD_transcript_variant		5
HSD11B2	ENST00000567684.2	n.128+1753C>G		intron_variant, non_coding_transcript_variant		3
HSD11B2	ENST00000569303.1	n.28-102C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82366 AN: 151428 Hom.: 25996 Cov.: 30

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.: 30 AF XY: 0.344 AC XY: 84 AN XY: 244

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.544 AC: 82484 AN: 151546 Hom.: 26056 Cov.: 30 AF XY: 0.543 AC XY: 40196 AN XY: 73996

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.506

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	10
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs56303414; hg19: chr16-67466435;