rs846911

Variant names:

• chr1-209702906-C-A
• rs846911
• NM_001206741.2:c.-48-1989C>A

Variant summary

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

The NM_181755.3(HSD11B1):​c.-26-2011C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 152,154 control chromosomes in the GnomAD database, including 1,862 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 0.089 (1862 hom., cov: 32)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_001206741.2		c.-48-1989C>A		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.-26-2011C>A		intron	N/A	NP_861420.1	P28845
	HSD11B1-AS1	NR_134509.1		n.96+21124G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-48-1989C>A		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000261465.5	TSL:5	c.-48-1989C>A		intron	N/A	ENSP00000261465.2	A0A0A0MQV1
	HSD11B1	ENST00000615289.4	TSL:5	c.-26-2011C>A		intron	N/A	ENSP00000478430.1	A0A087WU76

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13472 AN: 152036 Hom.: 1857 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.0630

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

GnomAD4 genome AF: 0.0888 AC: 13512 AN: 152154 Hom.: 1862 Cov.: 32 AF XY: 0.0865 AC XY: 6433 AN XY: 74396

African (AFR) AF: 0.293 AC: 12130 AN: 41448

American (AMR) AF: 0.0330 AC: 504 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5180

South Asian (SAS) AF: 0.0784 AC: 378 AN: 4820

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00262 AC: 178 AN: 68022

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0362 Hom.: 708

Bravo AF: 0.0976

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.76
PhyloP100		-0.0070
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: rs846911; hg19: chr1-209876251;