rs12086634
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005525.4(HSD11B1):c.332-29T>G 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 1,611,884 control chromosomes in the GnomAD database, including 33,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.20 ( 2972 hom., cov: 32)
Exomes 𝑓: 0.20 ( 30048 hom. )
Consequence
HSD11B1
NM_005525.4 intron
NM_005525.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.07
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 1-209706914-T-G is Benign according to our data. Variant chr1-209706914-T-G is described in ClinVar as [Benign]. Clinvar id is 375729.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD11B1 | NM_005525.4 | c.332-29T>G | intron_variant | ENST00000367027.5 | |||
HSD11B1-AS1 | NR_134510.1 | n.66+35583A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD11B1 | ENST00000367027.5 | c.332-29T>G | intron_variant | 1 | NM_005525.4 | P1 | |||
HSD11B1-AS1 | ENST00000441672.1 | n.96+17116A>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.196 AC: 29796AN: 152074Hom.: 2962 Cov.: 32
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GnomAD3 exomes AF: 0.206 AC: 51796AN: 250856Hom.: 5586 AF XY: 0.205 AC XY: 27736AN XY: 135552
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GnomAD4 exome AF: 0.200 AC: 292303AN: 1459692Hom.: 30048 Cov.: 32 AF XY: 0.199 AC XY: 144603AN XY: 726312
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GnomAD4 genome ? AF: 0.196 AC: 29838AN: 152192Hom.: 2972 Cov.: 32 AF XY: 0.197 AC XY: 14646AN XY: 74402
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cortisone reductase deficiency 2 Benign:1
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous c.331+94T>G variant in HSD11B1 has been identified in 3 individuals with cortisone reductase deficiency (PMID: 12858176). This variant is classified as benign for cortisone reductase deficiency because it has been identified in >25% of European (Finnish) chromosomes and 2719 total homozygotes by ExAC (http://gnomad.broadinstitute.org/). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at