rs1553266259
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_170707.4(LMNA):c.1609-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LMNA
NM_170707.4 splice_region, splice_polypyrimidine_tract, intron
NM_170707.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00007246
2
Clinical Significance
Conservation
PhyloP100: -0.739
Genes affected
LMNA (HGNC:6636): (lamin A/C) The protein encoded by this gene is part of the nuclear lamina, 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. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]
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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=-0.81).
BP6
?
Variant 1-156137650-C-T is Benign according to our data. Variant chr1-156137650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 543287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNA | NM_005572.4 | c.1609-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000677389.1 | |||
LMNA | NM_170707.4 | c.1609-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000368300.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.1609-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_170707.4 | P1 | |||
LMNA | ENST00000677389.1 | c.1609-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_005572.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1400272Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 690720
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1400272
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
690720
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 01, 2022 | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at