1-183103416-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_002293.4(LAMC1):c.507C>T(p.Asp169Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,614,170 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 (no stars).
Frequency
Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 0 hom. )
Consequence
LAMC1
NM_002293.4 synonymous
NM_002293.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.30
Genes affected
LAMC1 (HGNC:6492): (laminin subunit gamma 1) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also suggested that it had diverged considerably from the beta chain genes. Embryos of transgenic mice in which both alleles of the gamma 1 chain gene were inactivated by homologous recombination, lacked basement membranes, indicating that laminin, gamma 1 chain is necessary for laminin heterotrimer assembly. It has been inferred by analogy with the strikingly similar 3' UTR sequence in mouse laminin gamma 1 cDNA, that multiple polyadenylation sites are utilized in human to generate the 2 different sized mRNAs (5.5 and 7.5 kb) seen on Northern analysis. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 1-183103416-C-T is Benign according to our data. Variant chr1-183103416-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048970.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-4.3 with no splicing effect.
BS2
High AC in GnomAd4 at 81 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LAMC1 | ENST00000258341.5 | c.507C>T | p.Asp169Asp | synonymous_variant | Exon 2 of 28 | 1 | NM_002293.4 | ENSP00000258341.3 | ||
| LAMC1 | ENST00000484114 | c.-379C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 4 | 3 | ENSP00000473583.1 | ||||
| LAMC1 | ENST00000484114 | c.-379C>T | 5_prime_UTR_variant | Exon 2 of 4 | 3 | ENSP00000473583.1 |
Frequencies
GnomAD3 genomes 0.000532 AC: 81AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000529 AC: 133AN: 251408Hom.: 0 AF XY: 0.000574 AC XY: 78AN XY: 135884
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GnomAD4 exome AF: 0.000397 AC: 581AN: 1461864Hom.: 0 Cov.: 30 AF XY: 0.000444 AC XY: 323AN XY: 727230
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GnomAD4 genome 0.000532 AC: 81AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
LAMC1-related disorder Benign:1
Dec 05, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at