rs10735934

Variant names:

• chr12-40339098-C-A
• rs10735934
• NM_198578.4:c.5949-1196C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40339098-C-A
• chr12-40339098-C-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.5949-1196C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,022 control chromosomes in the GnomAD database, including 19,508 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 0.51 (19508 hom., cov: 33)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2	NM_198578.4	c.5949-1196C>A		intron_variant	Intron 40 of 50	ENST00000298910.12	NP_940980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12	c.5949-1196C>A		intron_variant	Intron 40 of 50	1	NM_198578.4	ENSP00000298910.7

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76843 AN: 151904 Hom.: 19504 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.506 AC: 76892 AN: 152022 Hom.: 19508 Cov.: 33 AF XY: 0.506 AC XY: 37565 AN XY: 74310

African (AFR) AF: 0.486 AC: 20142 AN: 41450

American (AMR) AF: 0.497 AC: 7596 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1802 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2338 AN: 5170

South Asian (SAS) AF: 0.589 AC: 2844 AN: 4826

European-Finnish (FIN) AF: 0.490 AC: 5181 AN: 10564

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35397 AN: 67954

Other (OTH) AF: 0.497 AC: 1046 AN: 2106

Alfa AF: 0.516 Hom.: 35304

Bravo AF: 0.500

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.70
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10735934; hg19: chr12-40732900;