rs936111

Variant names:

• chr15-101018931-A-G
• rs936111
• NM_024652.6:c.1610-2122A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRRK1	NM_024652.6	c.1610-2122A>G		intron_variant	Intron 12 of 33	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8	c.1610-2122A>G		intron_variant	Intron 12 of 33	5	NM_024652.6	ENSP00000373600.3
LRRK1	ENST00000525284.5	n.1610-2122A>G		intron_variant	Intron 11 of 32	1		ENSP00000433069.1
LRRK1	ENST00000531270.5	n.1610-2122A>G		intron_variant	Intron 11 of 31	1		ENSP00000431668.1

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

African (AFR) AF: 0.102 AC: 4242 AN: 41548

American (AMR) AF: 0.117 AC: 1791 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3472

East Asian (EAS) AF: 0.165 AC: 855 AN: 5192

South Asian (SAS) AF: 0.109 AC: 528 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1248 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9993 AN: 68022

Other (OTH) AF: 0.144 AC: 304 AN: 2114

Alfa AF: 0.141 Hom.: 2968

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
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs936111; hg19: chr15-101559136;