rs387907168
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP3_ModeratePP5BS2
The NM_005525.4(HSD11B1):c.409C>T(p.Arg137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
HSD11B1
NM_005525.4 missense
NM_005525.4 missense
Scores
7
3
5
Clinical Significance
Conservation
PhyloP100: 3.27
Genes affected
HSD11B1 (HGNC:5208): (hydroxysteroid 11-beta dehydrogenase 1) The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. Alternate splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.843
PP5
?
Variant 1-209707020-C-T is Pathogenic according to our data. Variant chr1-209707020-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 31588.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD11B1 | NM_005525.4 | c.409C>T | p.Arg137Cys | missense_variant | 4/6 | ENST00000367027.5 | |
HSD11B1-AS1 | NR_134510.1 | n.66+35477G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD11B1 | ENST00000367027.5 | c.409C>T | p.Arg137Cys | missense_variant | 4/6 | 1 | NM_005525.4 | P1 | |
HSD11B1-AS1 | ENST00000441672.1 | n.96+17010G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250832Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135528
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461558Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727100
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cortisone reductase deficiency 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 08, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;D;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.89, 0.89
MutPred
Gain of methylation at K138 (P = 0.028);Gain of methylation at K138 (P = 0.028);Gain of methylation at K138 (P = 0.028);Gain of methylation at K138 (P = 0.028);
MVP
MPC
1.0
ClinPred
D
GERP RS
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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