rs932335

Positions:

• chr1-209732389-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005525.4(HSD11B1):​c.518-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,609,338 control chromosomes in the GnomAD database, including 35,158 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 0.21 (3351 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31807 hom.)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.518-47G>C		intron_variant		ENST00000367027.5	NP_005516.1
HSD11B1	NM_001206741.2	c.518-47G>C		intron_variant			NP_001193670.1
HSD11B1	NM_181755.3	c.518-47G>C		intron_variant			NP_861420.1
HSD11B1-AS1	NR_134510.1	n.66+10108C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.518-47G>C		intron_variant		1	NM_005525.4	ENSP00000355994.3
HSD11B1	ENST00000367028.6	c.518-47G>C		intron_variant		5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.518-47G>C		intron_variant		5		ENSP00000261465.2
HSD11B1	ENST00000615289.4	c.518-47G>C		intron_variant		5		ENSP00000478430.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31553 AN: 151958 Hom.: 3345 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.211 AC: 52888 AN: 250454 Hom.: 5779 AF XY: 0.208 AC XY: 28230 AN XY: 135406

Gnomad AFR exome AF: 0.211

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.176

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.206 AC: 299877 AN: 1457262 Hom.: 31807 Cov.: 31 AF XY: 0.204 AC XY: 148201 AN XY: 725164

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.208 AC: 31589 AN: 152076 Hom.: 3351 Cov.: 32 AF XY: 0.208 AC XY: 15444 AN XY: 74358

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.194

Alfa AF: 0.212 Hom.: 658

Bravo AF: 0.205

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.63

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: rs932335; hg19: chr1-209905734; COSMIC: COSV54826466;