rs1491923

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2-DT	NR_186756.1	n.165-6921T>C		intron_variant	Intron 1 of 6
LRRK2-DT	NR_186757.1	n.164+26344T>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000416796.5	c.-63+542A>G		intron_variant	Intron 1 of 14	3		ENSP00000398726.1
LRRK2-DT	ENST00000412812.1	n.146-6921T>C		intron_variant	Intron 1 of 3	4
LINC02471	ENST00000641941.1	n.232-891A>G		intron_variant	Intron 1 of 6

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.321

Alfa AF: 0.338 Hom.: 4655

Bravo AF: 0.351

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1491923; hg19: chr12-40591117;