rs41286468
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_198578.4(LRRK2):c.364C>T(p.Leu122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,604,464 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L122L) has been classified as Likely benign.
Frequency
Consequence
NM_198578.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.364C>T | p.Leu122= | synonymous_variant | 4/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.364C>T | p.Leu122= | synonymous_variant | 4/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152064Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000279 AC: 70AN: 251234Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135810
GnomAD4 exome AF: 0.000238 AC: 346AN: 1452284Hom.: 0 Cov.: 29 AF XY: 0.000259 AC XY: 187AN XY: 723272
GnomAD4 genome AF: 0.000263 AC: 40AN: 152180Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74400
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | LRRK2: BP4, BP7 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at