chr1-209693771-A-G

Variant names:

• chr1-209693771-A-G
• rs10082248
• NM_001206741.2:c.-49+7486A>G

Variant summary

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

The NM_001206741.2(HSD11B1):​c.-49+7486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,268 control chromosomes in the GnomAD database, including 61,867 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 0.90 (61867 hom., cov: 32)
• Consequence: HSD11B1 NM_001206741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206741.2. 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+7486A>G		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.-27+7486A>G		intron	N/A	NP_861420.1
	HSD11B1-AS1	NR_134509.1		n.96+30259T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-49+7486A>G		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.-49+7486A>G		intron	N/A	ENSP00000261465.2
	HSD11B1	ENST00000615289.4	TSL:5	c.-27+7486A>G		intron	N/A	ENSP00000478430.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136711 AN: 152150 Hom.: 61825 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.899 AC: 136813 AN: 152268 Hom.: 61867 Cov.: 32 AF XY: 0.897 AC XY: 66767 AN XY: 74444

African (AFR) AF: 0.832 AC: 34536 AN: 41518

American (AMR) AF: 0.852 AC: 13022 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3331 AN: 3472

East Asian (EAS) AF: 0.687 AC: 3562 AN: 5188

South Asian (SAS) AF: 0.846 AC: 4084 AN: 4826

European-Finnish (FIN) AF: 0.976 AC: 10370 AN: 10624

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64845 AN: 68028

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.938 Hom.: 69083

Bravo AF: 0.889

Asia WGS AF: 0.786 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.082
DANN	Benign	0.49
PhyloP100		-2.2
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: rs10082248; hg19: chr1-209867116;