NM_005525.4:c.517+7245T>C

Variant names:

• chr1-209714373-T-C
• rs846906
• NM_005525.4:c.517+7245T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005525.4. 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_005525.4	MANE Select	c.517+7245T>C		intron	N/A	NP_005516.1	X5D2L1
	HSD11B1	NM_001206741.2		c.517+7245T>C		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.517+7245T>C		intron	N/A	NP_861420.1	P28845

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367027.5	TSL:1 MANE Select	c.517+7245T>C		intron	N/A	ENSP00000355994.3	P28845
	HSD11B1	ENST00000367028.6	TSL:5	c.517+7245T>C		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000966146.1		c.514+7245T>C		intron	N/A	ENSP00000636205.1

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

African (AFR) AF: 0.970 AC: 40330 AN: 41560

American (AMR) AF: 0.886 AC: 13550 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3220 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5188

South Asian (SAS) AF: 0.959 AC: 4622 AN: 4822

European-Finnish (FIN) AF: 0.841 AC: 8900 AN: 10588

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57155 AN: 68006

Other (OTH) AF: 0.889 AC: 1880 AN: 2114

Alfa AF: 0.859 Hom.: 110194

Bravo AF: 0.900

Asia WGS AF: 0.978 AC: 3400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.83
PhyloP100		0.10
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: rs846906; hg19: chr1-209887718;