1-209687323-T-C

Variant names:

• chr1-209687323-T-C
• rs2235543
• NM_001206741.2:c.-49+1038T>C

Variant summary

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

The NM_181755.3(HSD11B1):​c.-27+1038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,094 control chromosomes in the GnomAD database, including 46,530 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 0.77 (46530 hom., cov: 32)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 21 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181755.3. 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_001206741.2		c.-49+1038T>C		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.-27+1038T>C		intron	N/A	NP_861420.1
	HSD11B1-AS1	NR_134509.1		n.97-24262A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-49+1038T>C		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.-49+1038T>C		intron	N/A	ENSP00000261465.2
	HSD11B1	ENST00000615289.4	TSL:5	c.-27+1038T>C		intron	N/A	ENSP00000478430.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117232 AN: 151976 Hom.: 46510 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.771 AC: 117296 AN: 152094 Hom.: 46530 Cov.: 32 AF XY: 0.773 AC XY: 57486 AN XY: 74366

African (AFR) AF: 0.587 AC: 24302 AN: 41426

American (AMR) AF: 0.786 AC: 12007 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3099 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3241 AN: 5156

South Asian (SAS) AF: 0.703 AC: 3388 AN: 4816

European-Finnish (FIN) AF: 0.915 AC: 9702 AN: 10608

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58851 AN: 68018

Other (OTH) AF: 0.811 AC: 1715 AN: 2114

Alfa AF: 0.822 Hom.: 52812

Bravo AF: 0.758

Asia WGS AF: 0.684 AC: 2377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2235543; hg19: chr1-209860668;