rs1000283

Variant names:

• chr1-209721316-G-A
• rs1000283
• NM_005525.4:c.518-11120G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005525.4(HSD11B1):​c.518-11120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,742 control chromosomes in the GnomAD database, including 2,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2624 hom., cov: 30)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.737
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.518-11120G>A		intron_variant	Intron 4 of 5	ENST00000367027.5	NP_005516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.518-11120G>A		intron_variant	Intron 4 of 5	1	NM_005525.4	ENSP00000355994.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27606 AN: 151624 Hom.: 2619 Cov.: 30

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27636 AN: 151742 Hom.: 2624 Cov.: 30 AF XY: 0.183 AC XY: 13568 AN XY: 74150

African (AFR) AF: 0.137 AC: 5669 AN: 41352

American (AMR) AF: 0.174 AC: 2647 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 629 AN: 3464

East Asian (EAS) AF: 0.159 AC: 823 AN: 5160

South Asian (SAS) AF: 0.139 AC: 665 AN: 4794

European-Finnish (FIN) AF: 0.268 AC: 2812 AN: 10480

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13782 AN: 67936

Other (OTH) AF: 0.180 AC: 379 AN: 2102

Alfa AF: 0.193 Hom.: 1026

Bravo AF: 0.177

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.55
PhyloP100		0.74
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: rs1000283; hg19: chr1-209894661;