rs377386363

Variant names:

• chr15-100973841-C-A
• rs377386363
• NM_024652.6:c.135C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100973841-C-A
• chr15-100973841-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024652.6(LRRK1):​c.135C>A​(p.Gly45Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,141,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G45G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: LRRK1 NM_024652.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024652.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	NM_024652.6	MANE Select	c.135C>A	p.Gly45Gly	synonymous	Exon 3 of 34	NP_078928.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	ENST00000388948.8	TSL:5 MANE Select	c.135C>A	p.Gly45Gly	synonymous	Exon 3 of 34	ENSP00000373600.3	Q38SD2-1
	LRRK1	ENST00000532029.6	TSL:1	c.135C>A	p.Gly45Gly	synonymous	Exon 3 of 6	ENSP00000433268.2	Q38SD2-2
	LRRK1	ENST00000525284.5	TSL:1	n.135C>A		non_coding_transcript_exon	Exon 2 of 33	ENSP00000433069.1	E9PMK9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1141840 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 548084

African (AFR) AF: 0.00 AC: 0 AN: 23362

American (AMR) AF: 0.00 AC: 0 AN: 9290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15546

East Asian (EAS) AF: 0.00 AC: 0 AN: 26780

South Asian (SAS) AF: 0.0000260 AC: 1 AN: 38528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3100

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 949206

Other (OTH) AF: 0.00 AC: 0 AN: 45848

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.5
DANN	Benign	0.83
PhyloP100		-0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377386363; hg19: chr15-101514046;