chr16-67431412-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000196.4(HSD11B2):​c.164C>T​(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 1,131,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HSD11B2
NM_000196.4 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.588
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14763749).
BP6
Variant 16-67431412-C-T is Benign according to our data. Variant chr16-67431412-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3107081.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSD11B2NM_000196.4 linkuse as main transcriptc.164C>T p.Pro55Leu missense_variant 1/5 ENST00000326152.6 NP_000187.3
HSD11B2XM_047434048.1 linkuse as main transcriptc.-48+633C>T intron_variant XP_047290004.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSD11B2ENST00000326152.6 linkuse as main transcriptc.164C>T p.Pro55Leu missense_variant 1/51 NM_000196.4 ENSP00000316786 P1
ENST00000567261.1 linkuse as main transcriptn.53G>A non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000265
AC:
3
AN:
1131802
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
549576
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000411
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000832
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 30, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Benign
0.23
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.078
N
LIST_S2
Benign
0.60
T
M_CAP
Pathogenic
0.85
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
0.79
N
REVEL
Benign
0.15
Sift
Benign
0.73
T
Sift4G
Benign
0.68
T
Polyphen
0.0030
B
Vest4
0.12
MutPred
0.44
Loss of glycosylation at P55 (P = 0.0211);
MVP
0.60
MPC
0.53
ClinPred
0.060
T
GERP RS
-2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.039
gMVP
0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67465315; API