chr1-156114891-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_170707.4(LMNA):c.-28C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 1,484,916 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
LMNA
NM_170707.4 5_prime_UTR
NM_170707.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.893
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 1-156114891-C-T is Benign according to our data. Variant chr1-156114891-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 512853.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LMNA | NM_005572.4 | c.-28C>T | 5_prime_UTR_variant | 1/10 | ENST00000677389.1 | ||
LMNA | NM_170707.4 | c.-28C>T | 5_prime_UTR_variant | 1/12 | ENST00000368300.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LMNA | ENST00000368300.9 | c.-28C>T | 5_prime_UTR_variant | 1/12 | 1 | NM_170707.4 | P1 | ||
LMNA | ENST00000677389.1 | c.-28C>T | 5_prime_UTR_variant | 1/10 | NM_005572.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000865 AC: 1AN: 115592Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 61890
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GnomAD4 exome AF: 0.00000750 AC: 10AN: 1332702Hom.: 0 Cov.: 26 AF XY: 0.00000458 AC XY: 3AN XY: 655356
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74362
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 31, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
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