rs1388598

Positions:

• chr12-40222364-G-A
• chr12-40222364-G-C

Variant summary

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

The ENST00000412812.1(LRRK2-DT):​n.145+1295C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 151,746 control chromosomes in the GnomAD database, including 728 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 0.087 (728 hom., cov: 32)
• Consequence: LRRK2-DT ENST00000412812.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

Genes affected

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

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2-DT	ENST00000412812.1	n.145+1295C>T		intron_variant, non_coding_transcript_variant		4
LRRK2	ENST00000416796.5	c.-62-3191G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13191 AN: 151628 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0870 AC: 13200 AN: 151746 Hom.: 728 Cov.: 32 AF XY: 0.0870 AC XY: 6450 AN XY: 74114

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0756

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0424

Gnomad4 FIN AF: 0.0482

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0894

Bravo AF: 0.0969

Asia WGS AF: 0.0830 AC: 287 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1388598; hg19: chr12-40616166;