rs10735934

chr12-40339098-C-Achr12-40339098-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	UniProt
LRRK2	NM_198578.4	c.5949-1196C>A		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.5949-1196C>A		intron_variant		1	NM_198578.4	P1

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

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.497

Alfa AF: 0.517 Hom.: 26776

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10735934; hg19: chr12-40732900;