Variant 1-209705887-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_005525.4(HSD11B1):c.165G>A(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000786 in 1,614,040 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 (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 2 hom. )

Consequence

HSD11B1
NM_005525.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.20

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-209705887-G-A is Benign according to our data. Variant chr1-209705887-G-A is described in ClinVar as [Benign]. Clinvar id is 3048552.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BS2

High AC in GnomAd4 at 145 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4 link	c.165G>A	p.Ala55Ala	synonymous_variant	Exon 2 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.165G>A	p.Ala55Ala	synonymous_variant	Exon 2 of 6	1	NM_005525.4	ENSP00000355994.3		P28845

Frequencies

GnomAD3 genomes

AF:

0.000953

AC:

145

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

251132

Hom.:

AF XY:

0.00123

AC XY:

167

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000769

AC:

1124

AN:

1461720

Hom.:

Cov.:

AF XY:

0.000730

AC XY:

531

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00805

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000952

AC:

145

AN:

152320

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000543

Hom.:

Bravo

AF:

0.000283

EpiCase

AF:

0.000218

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HSD11B1-related disorder

Benign:1

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.1

DANN

Benign

0.79

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