rs11175593

Variant names:

• chr12-40208138-C-T
• rs11175593
• ENST00000416796.5:c.-63+11365C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000416796.5(LRRK2):​c.-63+11365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,248 control chromosomes in the GnomAD database, including 204 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 0.030 (204 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRK2 ENST00000416796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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]

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

LOC105369735 (HGNC:):

LRRK2-DT (HGNC:40848): (LRRK2 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369735	XR_007063560.1	n.451C>T		non_coding_transcript_exon_variant	Exon 2 of 2
LRRK2-DT	NR_186756.1	n.164+15521G>A		intron_variant	Intron 1 of 6
LRRK2-DT	NR_186757.1	n.164+15521G>A		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000416796.5	c.-63+11365C>T		intron_variant	Intron 1 of 14	3		ENSP00000398726.1
LINC02471	ENST00000641941.1	n.1471C>T		non_coding_transcript_exon_variant	Exon 7 of 7
LRRK2-DT	ENST00000412812.1	n.145+15521G>A		intron_variant	Intron 1 of 3	4
LINC02471	ENST00000661406.1	n.*10C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4556 AN: 152130 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0397

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 AFR exome AF: 0.00

GnomAD4 genome AF: 0.0299 AC: 4558 AN: 152248 Hom.: 204 Cov.: 33 AF XY: 0.0327 AC XY: 2434 AN XY: 74440

Gnomad4 AFR AF: 0.00660

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0640

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0299 Hom.: 293

Bravo AF: 0.0372

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11175593; hg19: chr12-40601940;