chr1-225401942-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002296.4(LBR):c.*1361T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,284 control chromosomes in the GnomAD database, including 854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.098 ( 854 hom., cov: 33)
Exomes 𝑓: 0.33 ( 0 hom. )
Consequence
LBR
NM_002296.4 3_prime_UTR
NM_002296.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.296
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 1-225401942-A-G is Benign according to our data. Variant chr1-225401942-A-G is described in ClinVar as [Benign]. Clinvar id is 295918.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LBR | NM_002296.4 | c.*1361T>C | 3_prime_UTR_variant | 14/14 | ENST00000272163.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LBR | ENST00000272163.9 | c.*1361T>C | 3_prime_UTR_variant | 14/14 | 1 | NM_002296.4 | P1 | ||
LBR | ENST00000338179.6 | c.*1361T>C | 3_prime_UTR_variant | 14/14 | 5 | P1 | |||
LBR | ENST00000651341.1 | c.*1114-214T>C | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0983 AC: 14958AN: 152162Hom.: 857 Cov.: 33
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GnomAD4 exome AF: 0.333 AC: 2AN: 6Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1AN XY: 4
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GnomAD4 genome ? AF: 0.0983 AC: 14965AN: 152278Hom.: 854 Cov.: 33 AF XY: 0.0949 AC XY: 7068AN XY: 74464
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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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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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