rs721709

Variant names:

• chr12-40315611-T-A
• rs721709
• NM_198578.4:c.4827+311T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40315611-T-A
• chr12-40315611-T-C
• chr12-40315611-T-G

Variant summary

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

The NM_198578.4(LRRK2):​c.4827+311T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,798 control chromosomes in the GnomAD database, including 37,320 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 0.70 (37320 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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

ENSG00000258167 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198578.4. 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
	LRRK2	NM_198578.4	MANE Select	c.4827+311T>A		intron	N/A	NP_940980.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK2	ENST00000298910.12	TSL:1 MANE Select	c.4827+311T>A		intron	N/A	ENSP00000298910.7
	LRRK2	ENST00000430804.5	TSL:1	n.*1500+311T>A		intron	N/A	ENSP00000410821.1
	LRRK2	ENST00000950031.1		c.4803+311T>A		intron	N/A	ENSP00000620090.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105879 AN: 151680 Hom.: 37285 Cov.: 31

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.698 AC: 105972 AN: 151798 Hom.: 37320 Cov.: 31 AF XY: 0.704 AC XY: 52245 AN XY: 74180

African (AFR) AF: 0.769 AC: 31855 AN: 41412

American (AMR) AF: 0.713 AC: 10843 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2119 AN: 3462

East Asian (EAS) AF: 0.508 AC: 2621 AN: 5158

South Asian (SAS) AF: 0.719 AC: 3466 AN: 4818

European-Finnish (FIN) AF: 0.781 AC: 8240 AN: 10556

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44633 AN: 67874

Other (OTH) AF: 0.670 AC: 1412 AN: 2108

Alfa AF: 0.698 Hom.: 4603

Bravo AF: 0.691

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.37
PhyloP100		1.0
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: rs721709; hg19: chr12-40709413; COSMIC: COSV54156266;