chr16-67431372-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000196.4(HSD11B2):c.124G>A(p.Ala42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,253,710 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00027 ( 3 hom. )
Consequence
HSD11B2
NM_000196.4 missense
NM_000196.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 0.753
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011157364).
BP6
Variant 16-67431372-G-A is Benign according to our data. Variant chr16-67431372-G-A is described in ClinVar as [Benign]. Clinvar id is 1989648.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSD11B2 | NM_000196.4 | c.124G>A | p.Ala42Thr | missense_variant | 1/5 | ENST00000326152.6 | NP_000187.3 | |
HSD11B2 | XM_047434048.1 | c.-48+593G>A | intron_variant | XP_047290004.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSD11B2 | ENST00000326152.6 | c.124G>A | p.Ala42Thr | missense_variant | 1/5 | 1 | NM_000196.4 | ENSP00000316786 | P1 | |
ENST00000567261.1 | n.93C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 62AN: 149604Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000958 AC: 42AN: 43840Hom.: 0 AF XY: 0.000999 AC XY: 26AN XY: 26034
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GnomAD4 exome AF: 0.000268 AC: 296AN: 1103998Hom.: 3 Cov.: 31 AF XY: 0.000285 AC XY: 153AN XY: 536820
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GnomAD4 genome AF: 0.000414 AC: 62AN: 149712Hom.: 0 Cov.: 31 AF XY: 0.000411 AC XY: 30AN XY: 73080
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 05, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.1585);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at