Variant chr1-209707020-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.27

Variant links:

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]

HSD11B1 links:

HSD11B1-AS1 (HGNC:54053): (HSD11B1 antisense RNA 1)

HSD11B1-AS1 links:

Genome browser will be placed here

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 linkuse as main transcript	c.409C>T	p.Arg137Cys	missense_variant	4/6	ENST00000367027.5
HSD11B1-AS1	NR_134510.1 linkuse as main transcript	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 linkuse as main transcript	c.409C>T	p.Arg137Cys	missense_variant	4/6	1	NM_005525.4	P1
HSD11B1-AS1	ENST00000441672.1 linkuse as main transcript	n.96+17010G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250832

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461558

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000493

Hom.:

Bravo

AF:

0.00000756

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;D;.;D

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.91

D;D;D;.

M_CAP

Benign

0.071

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Pathogenic

0.81

MutationAssessor

Uncertain

2.5

.;M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.7

.;D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.012

.;D;D;D

Sift4G

Uncertain

0.037

D;D;D;D

Polyphen

1.0

.;D;.;D

Vest4

0.89, 0.89

MutPred

0.61

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

0.95

MPC

1.0

ClinPred

0.99

GERP RS

5.0

Varity_R

0.72

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over