12-40308618-A-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_198578.4(LRRK2):c.4111A>G(p.Ile1371Val) variant causes a missense change. The variant allele was found at a frequency of 0.000808 in 1,614,078 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1371K) has been classified as Uncertain significance.
Frequency
Consequence
NM_198578.4 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 | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.4111A>G | p.Ile1371Val | missense_variant | 29/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.4111A>G | p.Ile1371Val | missense_variant | 29/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000650 AC: 99AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000865 AC: 217AN: 250952Hom.: 1 AF XY: 0.00105 AC XY: 142AN XY: 135610
GnomAD4 exome AF: 0.000824 AC: 1204AN: 1461724Hom.: 5 Cov.: 31 AF XY: 0.000891 AC XY: 648AN XY: 727162
GnomAD4 genome ? AF: 0.000656 AC: 100AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.000644 AC XY: 48AN XY: 74494
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:3Other:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Likely 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | LRRK2: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at