rs2288592
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_198129.4(LAMA3):c.9211-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,607,248 control chromosomes in the GnomAD database, including 317,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.51 ( 22805 hom., cov: 30)
Exomes 𝑓: 0.62 ( 294692 hom. )
Consequence
LAMA3
NM_198129.4 intron
NM_198129.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.09
Genes affected
LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 18-23946123-C-T is Benign according to our data. Variant chr18-23946123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA3 | NM_000227.6 | c.4384-21C>T | intron_variant | ENST00000269217.11 | |||
LAMA3 | NM_198129.4 | c.9211-21C>T | intron_variant | ENST00000313654.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA3 | ENST00000269217.11 | c.4384-21C>T | intron_variant | 1 | NM_000227.6 | ||||
LAMA3 | ENST00000313654.14 | c.9211-21C>T | intron_variant | 1 | NM_198129.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.514 AC: 78049AN: 151742Hom.: 22806 Cov.: 30
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GnomAD3 exomes AF: 0.534 AC: 134214AN: 251384Hom.: 40055 AF XY: 0.546 AC XY: 74132AN XY: 135862
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GnomAD4 exome AF: 0.622 AC: 905897AN: 1455388Hom.: 294692 Cov.: 33 AF XY: 0.620 AC XY: 449067AN XY: 724342
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GnomAD4 genome ? AF: 0.514 AC: 78061AN: 151860Hom.: 22805 Cov.: 30 AF XY: 0.506 AC XY: 37533AN XY: 74238
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Junctional epidermolysis bullosa, non-Herlitz type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Laryngo-onycho-cutaneous syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Junctional epidermolysis bullosa gravis of Herlitz Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at