rs146045042
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_002291.3(LAMB1):c.4183G>A(p.Glu1395Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,470,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002291.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB1 | NM_002291.3 | c.4183G>A | p.Glu1395Lys | missense_variant | 27/34 | ENST00000222399.11 | |
LAMB1 | XM_047420359.1 | c.4183G>A | p.Glu1395Lys | missense_variant | 27/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB1 | ENST00000222399.11 | c.4183G>A | p.Glu1395Lys | missense_variant | 27/34 | 1 | NM_002291.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000218 AC: 28AN: 128282Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000959 AC: 24AN: 250178Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135362
GnomAD4 exome AF: 0.000306 AC: 411AN: 1342138Hom.: 1 Cov.: 35 AF XY: 0.000279 AC XY: 186AN XY: 666782
GnomAD4 genome ? AF: 0.000218 AC: 28AN: 128334Hom.: 0 Cov.: 29 AF XY: 0.000133 AC XY: 8AN XY: 60314
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1395 of the LAMB1 protein (p.Glu1395Lys). This variant is present in population databases (rs146045042, gnomAD 0.02%). This missense change has been observed in individual(s) with LAMB1-related conditions (PMID: 25326635). ClinVar contains an entry for this variant (Variation ID: 561153). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cobblestone lissencephaly without muscular or ocular involvement Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it once in our laboratory in trans with another missense variant in a 5-year-old male with global delays, dysmorphisms, cortical dysplasia. Heterozygotes are expected to be asymptomatic carriers. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at