Variant chr1-209706914-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005525.4(HSD11B1):c.332-29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,611,884 control chromosomes in the GnomAD database, including 33,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 2972 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30048 hom. )

Consequence

HSD11B1
NM_005525.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.07

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-209706914-T-G is Benign according to our data. Variant chr1-209706914-T-G is described in ClinVar as [Benign]. Clinvar id is 375729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4 link	c.332-29T>G		intron_variant	Intron 3 of 5	ENST00000367027.5	NP_005516.1	P28845X5D2L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5 link	c.332-29T>G		intron_variant	Intron 3 of 5	1	NM_005525.4	ENSP00000355994.3		P28845

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29796

AN:

152074

Hom.:

2962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.206

AC:

51796

AN:

250856

Hom.:

5586

AF XY:

0.205

AC XY:

27736

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.200

AC:

292303

AN:

1459692

Hom.:

30048

Cov.:

AF XY:

0.199

AC XY:

144603

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.196

AC:

29838

AN:

152192

Hom.:

2972

Cov.:

AF XY:

0.197

AC XY:

14646

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.200

Hom.:

2803

Bravo

AF:

0.193

Asia WGS

AF:

0.208

AC:

724

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cortisone reductase deficiency 2

Benign:1

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

The heterozygous c.331+94T>G variant in HSD11B1 has been identified in 3 individuals with cortisone reductase deficiency (PMID: 12858176). This variant is classified as benign for cortisone reductase deficiency because it has been identified in >25% of European (Finnish) chromosomes and 2719 total homozygotes by ExAC (http://gnomad.broadinstitute.org/). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.9

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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