rs760951

Variant names:

• chr1-209688180-G-A
• rs760951
• NM_001206741.2:c.-49+1895G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-209688180-G-A
• chr1-209688180-G-C
• chr1-209688180-G-T

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+1895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,954 control chromosomes in the GnomAD database, including 45,044 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 0.75 (45044 hom., cov: 30)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 8 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=-0.84).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_001206741.2		c.-49+1895G>A		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.-27+1895G>A		intron	N/A	NP_861420.1
	HSD11B1-AS1	NR_134509.1		n.97-25119C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-49+1895G>A		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.-49+1895G>A		intron	N/A	ENSP00000261465.2
	HSD11B1	ENST00000615289.4	TSL:5	c.-27+1895G>A		intron	N/A	ENSP00000478430.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114539 AN: 151836 Hom.: 45025 Cov.: 30

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.754 AC: 114593 AN: 151954 Hom.: 45044 Cov.: 30 AF XY: 0.756 AC XY: 56192 AN XY: 74302

African (AFR) AF: 0.527 AC: 21791 AN: 41344

American (AMR) AF: 0.780 AC: 11921 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3096 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3217 AN: 5144

South Asian (SAS) AF: 0.702 AC: 3380 AN: 4816

European-Finnish (FIN) AF: 0.915 AC: 9683 AN: 10584

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

European-Non Finnish (NFE) AF: 0.865 AC: 58823 AN: 68002

Other (OTH) AF: 0.801 AC: 1691 AN: 2110

Alfa AF: 0.831 Hom.: 67112

Bravo AF: 0.739

Asia WGS AF: 0.680 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		1.5
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: rs760951; hg19: chr1-209861525;