rs199577453
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_032737.4(LMNB2):c.265-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0007 in 1,606,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00073 ( 0 hom. )
Consequence
LMNB2
NM_032737.4 intron
NM_032737.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.229
Genes affected
LMNB2 (HGNC:6638): (lamin B2) This gene encodes a B type nuclear lamin. The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Mutations in this gene are associated with acquired partial lipodystrophy. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 19-2444559-G-A is Benign according to our data. Variant chr19-2444559-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445837.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNB2 | NM_032737.4 | c.265-19C>T | intron_variant | ENST00000325327.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNB2 | ENST00000325327.4 | c.265-19C>T | intron_variant | 1 | NM_032737.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000453 AC: 69AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000571 AC: 140AN: 245218Hom.: 0 AF XY: 0.000600 AC XY: 80AN XY: 133356
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GnomAD4 exome AF: 0.000726 AC: 1056AN: 1454046Hom.: 0 Cov.: 36 AF XY: 0.000703 AC XY: 509AN XY: 723654
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GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.000444 AC XY: 33AN XY: 74388
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 02, 2017 | - - |
Progressive myoclonic epilepsy type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 27, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Lipodystrophy, partial, acquired, susceptibility to;C4225289:Progressive myoclonic epilepsy type 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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RBP_binding_hub_radar
RBP_regulation_power_radar
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