1-209731088-G-A

Position:

• chr1-209731088-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005525.4(HSD11B1):​c.518-1348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,188 control chromosomes in the GnomAD database, including 3,115 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 (3115 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1	NM_005525.4	c.518-1348G>A		intron_variant		ENST00000367027.5
HSD11B1-AS1	NR_134510.1	n.66+11409C>T		intron_variant, non_coding_transcript_variant
HSD11B1	NM_001206741.2	c.518-1348G>A		intron_variant
HSD11B1	NM_181755.3	c.518-1348G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1	ENST00000367027.5	c.518-1348G>A		intron_variant		1	NM_005525.4	P1
HSD11B1	ENST00000261465.5	c.518-1348G>A		intron_variant		5
HSD11B1	ENST00000367028.6	c.518-1348G>A		intron_variant		5		P1
HSD11B1	ENST00000615289.4	c.518-1348G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30340 AN: 152070 Hom.: 3108 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.200 AC: 30380 AN: 152188 Hom.: 3115 Cov.: 32 AF XY: 0.200 AC XY: 14869 AN XY: 74404

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.193

Alfa AF: 0.213 Hom.: 466

Bravo AF: 0.196

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.35

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: rs12060922; hg19: chr1-209904433;