rs11175655

chr12-40229925-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198578.4(LRRK2):c.238-2349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 141,882 control chromosomes in the GnomAD database, including 983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (983 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

LRRK2 (HGNC:18618): (leucine rich repeat kinase 2) This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4	c.238-2349G>A		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.238-2349G>A		intron_variant		1	NM_198578.4	P1
	ENST00000688991.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.103 AC: 14599 AN: 141848 Hom.: 978 Cov.: 31

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.00229

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0793

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 14627 AN: 141882 Hom.: 983 Cov.: 31 AF XY: 0.101 AC XY: 6945 AN XY: 68438

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.0730

Gnomad4 EAS AF: 0.00230

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0793

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0874

Alfa AF: 0.116 Hom.: 1563

Bravo AF: 0.0938

Asia WGS AF: 0.0760 AC: 262 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	7.5
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs11175655; hg19: chr12-40623727;