NM_000196.4:c.265+1019C>G

Variant names:

• chr16-67432532-C-G
• rs56303414
• NM_000196.4:c.265+1019C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000196.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B2	NM_000196.4	MANE Select	c.265+1019C>G		intron	N/A	NP_000187.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B2	ENST00000326152.6	TSL:1 MANE Select	c.265+1019C>G		intron	N/A	ENSP00000316786.5	P80365
	HSD11B2	ENST00000855497.1		c.265+1019C>G		intron	N/A	ENSP00000525556.1
	HSD11B2	ENST00000855496.1		c.265+1019C>G		intron	N/A	ENSP00000525555.1

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

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.379 AC: 103 AN: 272

Other (OTH) AF: 0.529 AC: 18 AN: 34

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

African (AFR) AF: 0.879 AC: 36300 AN: 41318

American (AMR) AF: 0.405 AC: 6179 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1693 AN: 3464

East Asian (EAS) AF: 0.169 AC: 866 AN: 5110

South Asian (SAS) AF: 0.515 AC: 2472 AN: 4800

European-Finnish (FIN) AF: 0.470 AC: 4911 AN: 10446

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28323 AN: 67864

Other (OTH) AF: 0.506 AC: 1065 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.60
PhyloP100		0.96
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

Other links and lift over

dbSNP: rs56303414; hg19: chr16-67466435;