rs117621658
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006059.4(LAMC3):c.3069+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,565,466 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0041 ( 10 hom. )
Consequence
LAMC3
NM_006059.4 intron
NM_006059.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00600
Genes affected
LAMC3 (HGNC:6494): (laminin subunit gamma 3) 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 are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form 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 3. The gamma 3 chain is most similar to the gamma 1 chain, and contains all the 6 domains expected of the gamma chain. It is a component of laminin 12. The gamma 3 chain is broadly expressed in skin, heart, lung, and the reproductive tracts. In skin, it is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. Gamma 3 is also a prominent element of the apical surface of ciliated epithelial cells of lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma 3-containing laminins along ciliated epithelial surfaces suggests that the apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells. [provided by RefSeq, Aug 2011]
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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=-0.86).
BP6
?
Variant 9-131069872-C-T is Benign according to our data. Variant chr9-131069872-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435731.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00297 (453/152344) while in subpopulation NFE AF= 0.00484 (329/68036). AF 95% confidence interval is 0.0044. There are 0 homozygotes in gnomad4. There are 203 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMC3 | NM_006059.4 | c.3069+22C>T | intron_variant | ENST00000361069.9 | |||
LAMC3 | XM_006716921.3 | c.3069+22C>T | intron_variant | ||||
LAMC3 | XM_011518121.2 | c.3069+22C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMC3 | ENST00000361069.9 | c.3069+22C>T | intron_variant | 2 | NM_006059.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00298 AC: 453AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00296 AC: 524AN: 177020Hom.: 3 AF XY: 0.00299 AC XY: 283AN XY: 94546
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GnomAD4 exome AF: 0.00409 AC: 5777AN: 1413122Hom.: 10 Cov.: 31 AF XY: 0.00401 AC XY: 2802AN XY: 698794
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GnomAD4 genome ? AF: 0.00297 AC: 453AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.00273 AC XY: 203AN XY: 74494
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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 | Genetic Services Laboratory, University of Chicago | May 19, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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