Genetic Variant HSD11B1:p.Gly107Glu (chr1-209706809-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005525.4(HSD11B1):c.320G>A(p.Gly107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G107A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSD11B1
NM_005525.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20510536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4 link	c.320G>A	p.Gly107Glu	missense_variant	Exon 3 of 6	ENST00000367027.5	NP_005516.1	P28845X5D2L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5 link	c.320G>A	p.Gly107Glu	missense_variant	Exon 3 of 6	1	NM_005525.4	ENSP00000355994.3		P28845

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727128

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0022

T;T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.65

T;T;T;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

-0.49

.;N;.;N

PrimateAI

Benign

0.45

PROVEAN

Benign

1.3

.;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.32

.;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.26

.;B;.;B

Vest4

0.38

MutPred

0.55

Loss of catalytic residue at A106 (P = 0.0281);Loss of catalytic residue at A106 (P = 0.0281);Loss of catalytic residue at A106 (P = 0.0281);Loss of catalytic residue at A106 (P = 0.0281);

MVP

0.36

MPC

0.31

ClinPred

0.55

GERP RS

3.2

Varity_R

0.35

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over