rs1388598

Variant names:

• chr12-40222364-G-A
• rs1388598
• ENST00000416796.5:c.-62-3191G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000416796.5(LRRK2):​c.-62-3191G>A variant causes a intron 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 ENST00000416796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 7 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRRK2-DT	NR_186756.1	n.164+1295C>T		intron_variant	Intron 1 of 6
LRRK2-DT	NR_186757.1	n.164+1295C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000416796.5	c.-62-3191G>A		intron_variant	Intron 1 of 14	3		ENSP00000398726.1
LRRK2-DT	ENST00000412812.2	n.237+1295C>T		intron_variant	Intron 1 of 3	4
LRRK2-DT	ENST00000783202.1	n.199+1295C>T		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.140 AC: 5800 AN: 41376

American (AMR) AF: 0.137 AC: 2093 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 262 AN: 3466

East Asian (EAS) AF: 0.102 AC: 528 AN: 5170

South Asian (SAS) AF: 0.0424 AC: 204 AN: 4810

European-Finnish (FIN) AF: 0.0482 AC: 504 AN: 10466

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3600 AN: 67898

Other (OTH) AF: 0.0894 AC: 188 AN: 2104

Alfa AF: 0.0526 Hom.: 118

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
PhyloP100		-0.0030

Splicing

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

Other links and lift over

dbSNP: rs1388598; hg19: chr12-40616166;