rs2034809

chr15-101015194-G-Achr15-101015194-G-Cchr15-101015194-G-T

Variant summary

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

The NM_024652.6(LRRK1):c.1533-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 679,346 control chromosomes in the GnomAD database, including 90,068 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 0.47 (17789 hom., cov: 32)
  • Exomes 𝑓: 0.52 (72279 hom.)
• Consequence: LRRK1 NM_024652.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.11

Genes affected

LRRK1 (HGNC:18608): (leucine rich repeat kinase 1) This gene encodes a multi-domain protein that is a leucine-rich repeat kinase and a GDP/GTP binding protein. The encoded protein is thought to play a role in the regulation of bone mass. Mice lacking a similar gene showed severe osteopetrosis, increased bone mineralization and decreased bone resorption. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK1	NM_024652.6	c.1533-132G>A		intron_variant		ENST00000388948.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK1	ENST00000388948.8	c.1533-132G>A		intron_variant		5	NM_024652.6	P1
LRRK1	ENST00000525284.5	c.1533-132G>A		intron_variant, NMD_transcript_variant		1
LRRK1	ENST00000531270.5	c.1533-132G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71447 AN: 151938 Hom.: 17779 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.515 AC: 271699 AN: 527290 Hom.: 72279 AF XY: 0.513 AC XY: 142103 AN XY: 276738

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.470 AC: 71496 AN: 152056 Hom.: 17789 Cov.: 32 AF XY: 0.477 AC XY: 35420 AN XY: 74328

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.513

Alfa AF: 0.490 Hom.: 22912

Bravo AF: 0.469

Asia WGS AF: 0.605 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.040
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2034809; hg19: chr15-101555399;