rs12060922

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.714
Variant links:
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]

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ACMG classification

Classification made for transcript

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
HSD11B1NM_005525.4 linkuse as main transcriptc.518-1348G>A intron_variant ENST00000367027.5
HSD11B1-AS1NR_134510.1 linkuse as main transcriptn.66+11409C>T intron_variant, non_coding_transcript_variant
HSD11B1NM_001206741.2 linkuse as main transcriptc.518-1348G>A intron_variant
HSD11B1NM_181755.3 linkuse as main transcriptc.518-1348G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSD11B1ENST00000367027.5 linkuse as main transcriptc.518-1348G>A intron_variant 1 NM_005525.4 P1
HSD11B1ENST00000261465.5 linkuse as main transcriptc.518-1348G>A intron_variant 5
HSD11B1ENST00000367028.6 linkuse as main transcriptc.518-1348G>A intron_variant 5 P1
HSD11B1ENST00000615289.4 linkuse as main transcriptc.518-1348G>A intron_variant 5

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12060922; hg19: chr1-209904433; API