NM_005525.4:c.331+53dupA

Variant names:

• chr1-209706871-C-CA
• rs45487298
• NM_005525.4:c.331+53dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.117
• Publications: 10 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_005525.4	MANE Select	c.331+53dupA		intron	N/A	NP_005516.1
	HSD11B1	NM_001206741.2		c.331+53dupA		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.331+53dupA		intron	N/A	NP_861420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367027.5	TSL:1 MANE Select	c.331+51_331+52insA		intron	N/A	ENSP00000355994.3
	HSD11B1	ENST00000367028.6	TSL:5	c.331+51_331+52insA		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.331+51_331+52insA		intron	N/A	ENSP00000261465.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29822 AN: 152020 Hom.: 2965 Cov.: 27

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

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.: 30 AF XY: 0.199 AC XY: 144282 AN XY: 724400

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

GnomAD4 genome AF: 0.196 AC: 29863 AN: 152138 Hom.: 2975 Cov.: 27 AF XY: 0.197 AC XY: 14654 AN XY: 74366

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: 40 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13672 AN: 67998

Other (OTH) AF: 0.190 AC: 402 AN: 2114

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45487298; hg19: chr1-209880216;