rs1491938

chr12-40251828-G-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.1181+284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,980 control chromosomes in the GnomAD database, including 18,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18236 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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=-0.91).
• BP6: Variant 12-40251828-G-A is Benign according to our data. Variant chr12-40251828-G-A is described in ClinVar as [Benign]. Clinvar id is 1250049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4	c.1181+284G>A		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.1181+284G>A		intron_variant		1	NM_198578.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72464 AN: 151860 Hom.: 18226 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.477 AC: 72504 AN: 151980 Hom.: 18236 Cov.: 31 AF XY: 0.471 AC XY: 34979 AN XY: 74262

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.465

Alfa AF: 0.560 Hom.: 37174

Bravo AF: 0.458

Asia WGS AF: 0.464 AC: 1608 AN: 3476

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

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.46
Dann	Benign	0.63

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: rs1491938; hg19: chr12-40645630;