chr1-209708028-G-T

Variant names:

• chr1-209708028-G-T
• rs11807619
• NM_005525.4:c.517+900G>T

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+900G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,124 control chromosomes in the GnomAD database, including 2,232 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 0.17 (2232 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.517+900G>T		intron_variant	Intron 4 of 5	ENST00000367027.5	NP_005516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.517+900G>T		intron_variant	Intron 4 of 5	1	NM_005525.4	ENSP00000355994.3

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25911 AN: 152006 Hom.: 2222 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.171 AC: 25952 AN: 152124 Hom.: 2232 Cov.: 32 AF XY: 0.171 AC XY: 12729 AN XY: 74356

African (AFR) AF: 0.171 AC: 7114 AN: 41506

American (AMR) AF: 0.168 AC: 2560 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1117 AN: 5180

South Asian (SAS) AF: 0.165 AC: 795 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10568

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

European-Non Finnish (NFE) AF: 0.163 AC: 11066 AN: 67982

Other (OTH) AF: 0.172 AC: 363 AN: 2108

Alfa AF: 0.133 Hom.: 407

Bravo AF: 0.172

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.3
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: rs11807619; hg19: chr1-209881373;