1-209732389-G-C

Variant names:

• chr1-209732389-G-C
• rs932335
• NM_005525.4:c.518-47G>C

Variant summary

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

The NM_005525.4(HSD11B1):​c.518-47G>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
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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.518-47G>C		intron	N/A	NP_005516.1
	HSD11B1	NM_001206741.2		c.518-47G>C		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.518-47G>C		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.518-47G>C		intron	N/A	ENSP00000355994.3
	HSD11B1	ENST00000367028.6	TSL:5	c.518-47G>C		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.518-47G>C		intron	N/A	ENSP00000261465.2

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

GnomAD2 exomes AF: 0.211 AC: 52888 AN: 250454 AF XY: 0.208

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 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

African (AFR) AF: 0.203 AC: 6790 AN: 33370

American (AMR) AF: 0.210 AC: 9386 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5315 AN: 26100

East Asian (EAS) AF: 0.169 AC: 6691 AN: 39638

South Asian (SAS) AF: 0.175 AC: 15084 AN: 86156

European-Finnish (FIN) AF: 0.271 AC: 14438 AN: 53234

Middle Eastern (MID) AF: 0.136 AC: 783 AN: 5762

European-Non Finnish (NFE) AF: 0.206 AC: 228628 AN: 1108120

Other (OTH) AF: 0.212 AC: 12762 AN: 60220

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

African (AFR) AF: 0.208 AC: 8642 AN: 41480

American (AMR) AF: 0.182 AC: 2786 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1037 AN: 5170

South Asian (SAS) AF: 0.171 AC: 825 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2860 AN: 10560

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14091 AN: 67968

Other (OTH) AF: 0.194 AC: 409 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		0.020
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: rs932335; hg19: chr1-209905734; COSMIC: COSV54826466;