1-209701909-A-G

Variant names:

• chr1-209701909-A-G
• rs846910
• NM_001206741.2:c.-48-2986A>G

Variant summary

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

The NM_181755.3(HSD11B1):​c.-26-3008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,148 control chromosomes in the GnomAD database, including 67,909 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 0.94 (67909 hom., cov: 31)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855
• Publications: 38 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 = 0.981 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.-48-2986A>G		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.-26-3008A>G		intron	N/A	NP_861420.1	P28845
	HSD11B1-AS1	NR_134509.1		n.96+22121T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-48-2986A>G		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000261465.5	TSL:5	c.-48-2986A>G		intron	N/A	ENSP00000261465.2	A0A0A0MQV1
	HSD11B1	ENST00000615289.4	TSL:5	c.-26-3008A>G		intron	N/A	ENSP00000478430.1	A0A087WU76

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143390 AN: 152030 Hom.: 67847 Cov.: 31

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.943 AC: 143510 AN: 152148 Hom.: 67909 Cov.: 31 AF XY: 0.940 AC XY: 69909 AN XY: 74376

African (AFR) AF: 0.989 AC: 41081 AN: 41538

American (AMR) AF: 0.884 AC: 13493 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3392 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3821 AN: 5140

South Asian (SAS) AF: 0.905 AC: 4351 AN: 4810

European-Finnish (FIN) AF: 0.935 AC: 9915 AN: 10600

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64303 AN: 68016

Other (OTH) AF: 0.951 AC: 2007 AN: 2110

Alfa AF: 0.938 Hom.: 92263

Bravo AF: 0.943

Asia WGS AF: 0.841 AC: 2927 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	4.3
DANN	Benign	0.84
PhyloP100		0.85
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: rs846910; hg19: chr1-209875254;