18-23857967-G-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_198129.4(LAMA3):āc.4260G>Cā(p.Gly1420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,780 control chromosomes in the GnomAD database, including 268,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.47 ( 19255 hom., cov: 32)
Exomes š: 0.57 ( 249510 hom. )
Consequence
LAMA3
NM_198129.4 synonymous
NM_198129.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.294
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 18-23857967-G-C is Benign according to our data. Variant chr18-23857967-G-C is described in ClinVar as [Benign]. Clinvar id is 403026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-23857967-G-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.294 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA3 | NM_198129.4 | c.4260G>C | p.Gly1420= | synonymous_variant | 33/75 | ENST00000313654.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA3 | ENST00000313654.14 | c.4260G>C | p.Gly1420= | synonymous_variant | 33/75 | 1 | NM_198129.4 | P1 | |
LAMA3 | ENST00000399516.7 | c.4260G>C | p.Gly1420= | synonymous_variant | 33/74 | 1 | |||
LAMA3 | ENST00000649721.1 | c.1152G>C | p.Gly384= | synonymous_variant | 8/48 |
Frequencies
GnomAD3 genomes AF: 0.475 AC: 72109AN: 151944Hom.: 19256 Cov.: 32
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GnomAD3 exomes AF: 0.494 AC: 123290AN: 249472Hom.: 33728 AF XY: 0.504 AC XY: 68245AN XY: 135356
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GnomAD4 exome AF: 0.572 AC: 836700AN: 1461716Hom.: 249510 Cov.: 56 AF XY: 0.570 AC XY: 414610AN XY: 727180
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GnomAD4 genome AF: 0.474 AC: 72119AN: 152064Hom.: 19255 Cov.: 32 AF XY: 0.466 AC XY: 34615AN XY: 74338
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
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 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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