1-209699245-A-G

Variant names:

• chr1-209699245-A-G
• rs10863782
• NM_001206741.2:c.-48-5650A>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.-26-5672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,732 control chromosomes in the GnomAD database, including 40,520 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 0.71 (40520 hom., cov: 29)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.825 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.-48-5650A>G		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.-26-5672A>G		intron	N/A	NP_861420.1	P28845
	HSD11B1-AS1	NR_134509.1		n.96+24785T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-48-5650A>G		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000261465.5	TSL:5	c.-48-5650A>G		intron	N/A	ENSP00000261465.2	A0A0A0MQV1
	HSD11B1	ENST00000615289.4	TSL:5	c.-26-5672A>G		intron	N/A	ENSP00000478430.1	A0A087WU76

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108000 AN: 151614 Hom.: 40518 Cov.: 29

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.712 AC: 108034 AN: 151732 Hom.: 40520 Cov.: 29 AF XY: 0.713 AC XY: 52814 AN XY: 74100

African (AFR) AF: 0.462 AC: 19081 AN: 41292

American (AMR) AF: 0.769 AC: 11744 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3084 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3098 AN: 5132

South Asian (SAS) AF: 0.694 AC: 3328 AN: 4796

European-Finnish (FIN) AF: 0.824 AC: 8667 AN: 10524

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56465 AN: 67946

Other (OTH) AF: 0.772 AC: 1622 AN: 2100

Alfa AF: 0.796 Hom.: 208837

Bravo AF: 0.699

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.086
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: rs10863782; hg19: chr1-209872590; COSMIC: COSV54829814;