rs538726706
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001105206.3(LAMA4):āc.1988T>Cā(p.Ile663Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,613,268 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.1988T>C | p.Ile663Thr | missense_variant | 16/39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.1988T>C | p.Ile663Thr | missense_variant | 16/39 | 1 | NM_001105206.3 | ENSP00000230538.7 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152180Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000661 AC: 166AN: 251194Hom.: 2 AF XY: 0.000913 AC XY: 124AN XY: 135746
GnomAD4 exome AF: 0.000338 AC: 494AN: 1460970Hom.: 5 Cov.: 29 AF XY: 0.000472 AC XY: 343AN XY: 726896
GnomAD4 genome AF: 0.000210 AC: 32AN: 152298Hom.: 1 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74464
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 06, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 26, 2013 | Ile656Thr in exon 16 of LAMA4: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, 3 mammals (opossum, Tasmanian devil, and wallaby) and parrot have a threonin e (Thr) at this position despite high nearby amino acid conservation. In additio n, computational analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high lik elihood of impact to the protein. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Dilated cardiomyopathy 1JJ Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 17, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at