1-209714373-T-C

Variant summary

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

The NM_005525.4(HSD11B1):c.517+7245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,244 control chromosomes in the GnomAD database, including 60,931 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 0.89 (60931 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1	NM_005525.4	c.517+7245T>C		intron_variant		ENST00000367027.5
HSD11B1-AS1	NR_134510.1	n.66+28124A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1	ENST00000367027.5	c.517+7245T>C		intron_variant		1	NM_005525.4	P1
HSD11B1-AS1	ENST00000441672.1	n.96+9657A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135702 AN: 152126 Hom.: 60871 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.892 AC: 135821 AN: 152244 Hom.: 60931 Cov.: 32 AF XY: 0.893 AC XY: 66479 AN XY: 74418

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.889

Alfa AF: 0.857 Hom.: 80650

Bravo AF: 0.900

Asia WGS AF: 0.978 AC: 3400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	5.7
Dann	Benign	0.83

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: rs846906; hg19: chr1-209887718;