NM_005525.4:c.517+572A>G

Variant names:

• chr1-209707700-A-G
• rs2236902
• NM_005525.4:c.517+572A>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+572A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 152,088 control chromosomes in the GnomAD database, including 541 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 0.039 (541 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.517+572A>G		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+572A>G		intron_variant	Intron 4 of 5	1	NM_005525.4	ENSP00000355994.3

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5967 AN: 151970 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.00578

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0392 AC: 5969 AN: 152088 Hom.: 541 Cov.: 32 AF XY: 0.0452 AC XY: 3363 AN XY: 74352

African (AFR) AF: 0.00576 AC: 239 AN: 41504

American (AMR) AF: 0.174 AC: 2657 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3464

East Asian (EAS) AF: 0.286 AC: 1471 AN: 5146

South Asian (SAS) AF: 0.100 AC: 483 AN: 4824

European-Finnish (FIN) AF: 0.0126 AC: 133 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 835 AN: 67984

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0287 Hom.: 372

Bravo AF: 0.0502

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.61
PhyloP100		0.54
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: rs2236902; hg19: chr1-209881045;