rs4844488

Positions:

• chr1-209712164-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.517+5036A>G		intron_variant		ENST00000367027.5	NP_005516.1
HSD11B1-AS1	NR_134510.1	n.66+30333T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.517+5036A>G		intron_variant		1	NM_005525.4	ENSP00000355994	P1
HSD11B1-AS1	ENST00000441672.1	n.96+11866T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0534 Hom.: 557

Bravo AF: 0.0681

Asia WGS AF: 0.158 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs4844488; hg19: chr1-209885509;