Genetic Variant HSD11B1:c.331+53dupA (chr1-209706871-C-CA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005525.4(HSD11B1):c.331+53dupA 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 1,607,542 control chromosomes in the GnomAD database, including 32,985 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 2975 hom., cov: 27)

Exomes 𝑓: 0.20 ( 30010 hom. )

Consequence

HSD11B1
NM_005525.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.117

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-209706871-C-CA is Benign according to our data. Variant chr1-209706871-C-CA is described in ClinVar as Benign. ClinVar VariationId is 375731.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4 link	c.331+53dupA		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.331+51_331+52insA		intron_variant	Intron 3 of 5	1	NM_005525.4	ENSP00000355994.3		P28845

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29822

AN:

152020

Hom.:

2965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.207

AC:

51922

AN:

250970

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.200

AC:

291594

AN:

1455404

Hom.:

30010

Cov.:

AF XY:

0.199

AC XY:

144282

AN XY:

724400

show subpopulations

African (AFR)

AF:

0.175

AC:

5830

AN:

33354

American (AMR)

AF:

0.208

AC:

9301

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5513

AN:

26102

East Asian (EAS)

AF:

0.183

AC:

7257

AN:

39666

South Asian (SAS)

AF:

0.176

AC:

15122

AN:

86104

European-Finnish (FIN)

AF:

0.263

AC:

14037

AN:

53420

Middle Eastern (MID)

AF:

0.136

AC:

781

AN:

5752

European-Non Finnish (NFE)

AF:

0.200

AC:

221358

AN:

1106128

Other (OTH)

AF:

0.206

AC:

12395

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14033

28066

42100

56133

70166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7698

15396

23094

30792

38490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29863

AN:

152138

Hom.:

2975

Cov.:

AF XY:

0.197

AC XY:

14654

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.179

AC:

7427

AN:

41508

American (AMR)

AF:

0.176

AC:

2698

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

729

AN:

3468

East Asian (EAS)

AF:

0.216

AC:

1118

AN:

5168

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4820

European-Finnish (FIN)

AF:

0.263

AC:

2781

AN:

10566

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13672

AN:

67998

Other (OTH)

AF:

0.190

AC:

402

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1211

2422

3632

4843

6054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.205

Hom.:

598

Bravo

AF:

0.193

Asia WGS

AF:

0.211

AC:

734

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cortisone reductase deficiency 2

Benign:1

Jan 23, 2024

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-209706871-CA-CAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over