rs1491942

chr12-40227006-C-G

Variant summary

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

The NM_198578.4(LRRK2):c.237+1366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,852 control chromosomes in the GnomAD database, including 4,238 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 0.23 (4238 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4	c.237+1366C>G		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.237+1366C>G		intron_variant		1	NM_198578.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34603 AN: 151736 Hom.: 4219 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.228 AC: 34671 AN: 151852 Hom.: 4238 Cov.: 31 AF XY: 0.230 AC XY: 17043 AN XY: 74224

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.211

Alfa AF: 0.208 Hom.: 444

Bravo AF: 0.243

Asia WGS AF: 0.352 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.7
Dann	Benign	0.42

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: rs1491942; hg19: chr12-40620808;