rs4844488

Variant names:

• chr1-209712164-A-G
• rs4844488
• NM_005525.4:c.517+5036A>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+5036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,278 control chromosomes in the GnomAD database, including 679 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 0.061 (679 hom., cov: 33)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 11 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 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+5036A>G		intron	N/A	NP_005516.1	X5D2L1
	HSD11B1	NM_001206741.2		c.517+5036A>G		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.517+5036A>G		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+5036A>G		intron	N/A	ENSP00000355994.3	P28845
	HSD11B1	ENST00000367028.6	TSL:5	c.517+5036A>G		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000966146.1		c.514+5036A>G		intron	N/A	ENSP00000636205.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9266 AN: 152160 Hom.: 677 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0609 AC: 9269 AN: 152278 Hom.: 679 Cov.: 33 AF XY: 0.0667 AC XY: 4965 AN XY: 74466

African (AFR) AF: 0.0107 AC: 444 AN: 41562

American (AMR) AF: 0.183 AC: 2801 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1499 AN: 5176

South Asian (SAS) AF: 0.103 AC: 496 AN: 4824

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0462 AC: 3141 AN: 68020

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0566 Hom.: 1443

Bravo AF: 0.0681

Asia WGS AF: 0.158 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.87
PhyloP100		-0.85
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: rs4844488; hg19: chr1-209885509;