1-225402534-T-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_002296.4(LBR):c.*769A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 152,718 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0075 ( 10 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 0 hom. )
Consequence
LBR
NM_002296.4 3_prime_UTR
NM_002296.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.514
Genes affected
LBR (HGNC:6518): (lamin B receptor) The protein encoded by this gene belongs to the ERG4/ERG24 family. It localized in the nuclear envelope inner membrane and anchors the lamina and the heterochromatin to the membrane. It may mediate interaction between chromatin and lamin B. Mutations of this gene has been associated with autosomal recessive HEM/Greenberg skeletal dysplasia. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
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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=-0.2).
BP6
?
Variant 1-225402534-T-A is Benign according to our data. Variant chr1-225402534-T-A is described in ClinVar as [Benign]. Clinvar id is 295923.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00751 (1144/152282) while in subpopulation SAS AF= 0.0172 (83/4834). AF 95% confidence interval is 0.0142. There are 10 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LBR | NM_002296.4 | c.*769A>T | 3_prime_UTR_variant | 14/14 | ENST00000272163.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LBR | ENST00000272163.9 | c.*769A>T | 3_prime_UTR_variant | 14/14 | 1 | NM_002296.4 | P1 | ||
LBR | ENST00000338179.6 | c.*769A>T | 3_prime_UTR_variant | 14/14 | 5 | P1 | |||
LBR | ENST00000651341.1 | c.*1113+670A>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00742 AC: 1129AN: 152166Hom.: 6 Cov.: 33
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GnomAD4 exome AF: 0.00229 AC: 1AN: 436Hom.: 0 Cov.: 0 AF XY: 0.00379 AC XY: 1AN XY: 264
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GnomAD4 genome ? AF: 0.00751 AC: 1144AN: 152282Hom.: 10 Cov.: 33 AF XY: 0.00752 AC XY: 560AN XY: 74462
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Greenberg dysplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at