NM_005525.4:c.517+10977T>G

Variant names:

• chr1-209718105-T-G
• rs11808690
• NM_005525.4:c.517+10977T>G

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+10977T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,042 control chromosomes in the GnomAD database, including 2,965 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 0.20 (2965 hom., cov: 31)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_005525.4	MANE Select	c.517+10977T>G		intron	N/A	NP_005516.1
	HSD11B1	NM_001206741.2		c.517+10977T>G		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.517+10977T>G		intron	N/A	NP_861420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367027.5	TSL:1 MANE Select	c.517+10977T>G		intron	N/A	ENSP00000355994.3
	HSD11B1	ENST00000367028.6	TSL:5	c.517+10977T>G		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000966146.1		c.514+10977T>G		intron	N/A	ENSP00000636205.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29699 AN: 151924 Hom.: 2956 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.196 AC: 29740 AN: 152042 Hom.: 2965 Cov.: 31 AF XY: 0.196 AC XY: 14602 AN XY: 74316

African (AFR) AF: 0.177 AC: 7331 AN: 41494

American (AMR) AF: 0.176 AC: 2691 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5170

South Asian (SAS) AF: 0.169 AC: 815 AN: 4818

European-Finnish (FIN) AF: 0.264 AC: 2778 AN: 10528

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13681 AN: 67976

Other (OTH) AF: 0.190 AC: 401 AN: 2112

Alfa AF: 0.208 Hom.: 449

Bravo AF: 0.192

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.9
DANN	Benign	0.36
PhyloP100		-0.88
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: rs11808690; hg19: chr1-209891450;