rs4965778
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_024652.6(LRRK1):āc.3447A>Gā(p.Thr1149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,162 control chromosomes in the GnomAD database, including 140,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.37 ( 12154 hom., cov: 33)
Exomes š: 0.41 ( 127960 hom. )
Consequence
LRRK1
NM_024652.6 synonymous
NM_024652.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.42
Genes affected
LRRK1 (HGNC:18608): (leucine rich repeat kinase 1) This gene encodes a multi-domain protein that is a leucine-rich repeat kinase and a GDP/GTP binding protein. The encoded protein is thought to play a role in the regulation of bone mass. Mice lacking a similar gene showed severe osteopetrosis, increased bone mineralization and decreased bone resorption. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 15-101051718-A-G is Benign according to our data. Variant chr15-101051718-A-G is described in ClinVar as [Benign]. Clinvar id is 1601184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.42 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK1 | NM_024652.6 | c.3447A>G | p.Thr1149= | synonymous_variant | 24/34 | ENST00000388948.8 | |
LOC105371026 | XR_001751726.2 | n.1051-939T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK1 | ENST00000388948.8 | c.3447A>G | p.Thr1149= | synonymous_variant | 24/34 | 5 | NM_024652.6 | P1 | |
LRRK1 | ENST00000525284.5 | c.*1380A>G | 3_prime_UTR_variant, NMD_transcript_variant | 23/33 | 1 | ||||
LRRK1 | ENST00000531270.5 | c.*1211A>G | 3_prime_UTR_variant, NMD_transcript_variant | 22/32 | 1 | ||||
ENST00000559857.1 | n.673-939T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.368 AC: 55982AN: 151974Hom.: 12159 Cov.: 33
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GnomAD3 exomes AF: 0.458 AC: 113567AN: 248140Hom.: 28788 AF XY: 0.452 AC XY: 60887AN XY: 134654
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GnomAD4 exome AF: 0.409 AC: 597200AN: 1461070Hom.: 127960 Cov.: 53 AF XY: 0.410 AC XY: 297649AN XY: 726808
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GnomAD4 genome ? AF: 0.368 AC: 56000AN: 152092Hom.: 12154 Cov.: 33 AF XY: 0.382 AC XY: 28443AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
LRRK1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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