rs1491941

Variant names:

• chr12-40227013-G-A
• rs1491941
• NM_198578.4:c.237+1373G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40227013-G-A
• chr12-40227013-G-C
• chr12-40227013-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198578.4(LRRK2):​c.237+1373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,772 control chromosomes in the GnomAD database, including 29,813 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 0.62 (29813 hom., cov: 30)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 7 publications found

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]

LRRK2 Gene-Disease associations (from GenCC):

• autosomal dominant Parkinson disease 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2	NM_198578.4	c.237+1373G>A		intron_variant	Intron 2 of 50	ENST00000298910.12	NP_940980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12	c.237+1373G>A		intron_variant	Intron 2 of 50	1	NM_198578.4	ENSP00000298910.7

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94553 AN: 151656 Hom.: 29775 Cov.: 30

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.624 AC: 94644 AN: 151772 Hom.: 29813 Cov.: 30 AF XY: 0.619 AC XY: 45897 AN XY: 74180

African (AFR) AF: 0.559 AC: 23088 AN: 41308

American (AMR) AF: 0.597 AC: 9098 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2286 AN: 3466

East Asian (EAS) AF: 0.687 AC: 3535 AN: 5142

South Asian (SAS) AF: 0.792 AC: 3814 AN: 4816

European-Finnish (FIN) AF: 0.529 AC: 5580 AN: 10550

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45047 AN: 67928

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.636 Hom.: 6217

Bravo AF: 0.626

Asia WGS AF: 0.738 AC: 2563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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: rs1491941; hg19: chr12-40620815;