1-209706871-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005525.4(HSD11B1):c.331+53dup 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

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

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
HSD11B1	NM_005525.4	c.331+53dup		intron_variant		ENST00000367027.5
HSD11B1-AS1	NR_134510.1	n.66+35625_66+35626insT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1	ENST00000367027.5	c.331+53dup		intron_variant		1	NM_005525.4	P1
HSD11B1-AS1	ENST00000441672.1	n.96+17158_96+17159insT		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.207 AC: 51922 AN: 250970 Hom.: 5608 AF XY: 0.205 AC XY: 27794 AN XY: 135614

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 SAS exome AF: 0.175

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

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.206

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

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.190

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

Benign, criteria provided, single submitter

clinical testing

Mendelics

Jan 23, 2024

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs45487298; hg19: chr1-209880216;