NM_001206741.2:c.-48-5650A>G

Variant names:

• chr1-209699245-A-G
• rs10863782
• NM_001206741.2:c.-48-5650A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206741.2(HSD11B1):​c.-48-5650A>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_001206741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_001206741.2	c.-48-5650A>G		intron_variant	Intron 1 of 6		NP_001193670.1
HSD11B1	NM_181755.3	c.-26-5672A>G		intron_variant	Intron 1 of 6		NP_861420.1
HSD11B1-AS1	NR_134509.1	n.96+24785T>C		intron_variant	Intron 1 of 2
HSD11B1-AS1	NR_134510.1	n.67-36184T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367028.6	c.-48-5650A>G		intron_variant	Intron 1 of 6	5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.-48-5650A>G		intron_variant	Intron 1 of 6	5		ENSP00000261465.2
HSD11B1	ENST00000615289.4	c.-26-5672A>G		intron_variant	Intron 1 of 5	5		ENSP00000478430.1
HSD11B1-AS1	ENST00000441672.1	n.96+24785T>C		intron_variant	Intron 1 of 2	3

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.772

Alfa AF: 0.815 Hom.: 102472

Bravo AF: 0.699

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs10863782; hg19: chr1-209872590; COSMIC: COSV54829814;