rs11175966

chr12-40309350-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198578.4(LRRK2):c.4317+117C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,311,974 control chromosomes in the GnomAD database, including 27,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2246 hom., cov: 32)
  • Exomes 𝑓: 0.20 (24977 hom.)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-40309350-C-A is Benign according to our data. Variant chr12-40309350-C-A is described in ClinVar as [Benign]. Clinvar id is 1279653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4	c.4317+117C>A		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.4317+117C>A		intron_variant		1	NM_198578.4	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23496 AN: 151726 Hom.: 2247 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.203 AC: 235354 AN: 1160130 Hom.: 24977 AF XY: 0.202 AC XY: 116023 AN XY: 574466

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.155 AC: 23505 AN: 151844 Hom.: 2246 Cov.: 32 AF XY: 0.150 AC XY: 11170 AN XY: 74238

Gnomad4 AFR AF: 0.0484

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.194

Alfa AF: 0.168 Hom.: 304

Bravo AF: 0.156

Asia WGS AF: 0.141 AC: 494 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.059
Dann	Benign	0.81

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: rs11175966; hg19: chr12-40703152;