chr18-23714058-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_198129.4(LAMA3):c.433T>C(p.Leu145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,022 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0072 ( 10 hom., cov: 30)
Exomes 𝑓: 0.00082 ( 12 hom. )
Consequence
LAMA3
NM_198129.4 synonymous
NM_198129.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.546
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 18-23714058-T-C is Benign according to our data. Variant chr18-23714058-T-C is described in ClinVar as [Benign]. Clinvar id is 1666850.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.546 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (1098/152152) while in subpopulation AFR AF= 0.0247 (1026/41476). AF 95% confidence interval is 0.0235. There are 10 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA3 | NM_198129.4 | c.433T>C | p.Leu145= | synonymous_variant | 2/75 | ENST00000313654.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA3 | ENST00000313654.14 | c.433T>C | p.Leu145= | synonymous_variant | 2/75 | 1 | NM_198129.4 | P1 | |
LAMA3 | ENST00000399516.7 | c.433T>C | p.Leu145= | synonymous_variant | 2/74 | 1 | |||
LAMA3 | ENST00000585600.5 | c.433T>C | p.Leu145= | synonymous_variant | 2/13 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00722 AC: 1097AN: 152034Hom.: 10 Cov.: 30
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GnomAD3 exomes AF: 0.00200 AC: 500AN: 249504Hom.: 7 AF XY: 0.00160 AC XY: 217AN XY: 135368
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GnomAD4 exome AF: 0.000823 AC: 1203AN: 1461870Hom.: 12 Cov.: 34 AF XY: 0.000732 AC XY: 532AN XY: 727240
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 03, 2022 | - - |
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