rs1491923

Variant names:

• chr12-40197315-A-G
• rs1491923
• ENST00000416796.5:c.-63+542A>G

Variant summary

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

The ENST00000416796.5(LRRK2):​c.-63+542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,070 control chromosomes in the GnomAD database, including 9,516 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 0.35 (9516 hom., cov: 32)
• Consequence: LRRK2 ENST00000416796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 20 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-DT (HGNC:40848): (LRRK2 divergent transcript)

LINC02471 (HGNC:53410): (long intergenic non-protein coding RNA 2471)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416796.5. 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-DT	NR_186756.1		n.165-6921T>C		intron	N/A
	LRRK2-DT	NR_186757.1		n.164+26344T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK2	ENST00000416796.5	TSL:3	c.-63+542A>G		intron	N/A	ENSP00000398726.1	C9JBF0
	LRRK2-DT	ENST00000412812.2	TSL:4	n.238-6921T>C		intron	N/A
	LINC02471	ENST00000641941.1		n.232-891A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53238 AN: 151952 Hom.: 9491 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.351 AC: 53307 AN: 152070 Hom.: 9516 Cov.: 32 AF XY: 0.357 AC XY: 26525 AN XY: 74338

African (AFR) AF: 0.353 AC: 14670 AN: 41504

American (AMR) AF: 0.416 AC: 6344 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1964 AN: 5168

South Asian (SAS) AF: 0.404 AC: 1945 AN: 4818

European-Finnish (FIN) AF: 0.413 AC: 4361 AN: 10566

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21710 AN: 67964

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.337 Hom.: 5124

Bravo AF: 0.351

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.74
PhyloP100		-0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1491923;

hg19: chr12-40591117;