rs936111

chr15-101018931-A-G

Variant summary

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

The NM_024652.6(LRRK1):c.1610-2122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,294 control chromosomes in the GnomAD database, including 1,337 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 0.13 (1337 hom., cov: 33)
• Consequence: LRRK1 NM_024652.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK1	NM_024652.6	c.1610-2122A>G		intron_variant		ENST00000388948.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK1	ENST00000388948.8	c.1610-2122A>G		intron_variant		5	NM_024652.6	P1
LRRK1	ENST00000525284.5	c.1610-2122A>G		intron_variant, NMD_transcript_variant		1
LRRK1	ENST00000531270.5	c.1610-2122A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19543 AN: 152176 Hom.: 1338 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.128 AC: 19549 AN: 152294 Hom.: 1337 Cov.: 33 AF XY: 0.123 AC XY: 9179 AN XY: 74460

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.144

Alfa AF: 0.144 Hom.: 2238

Bravo AF: 0.126

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	8.3
Dann	Benign	0.85

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: rs936111; hg19: chr15-101559136;