rs41319544

Variant names:

• chr15-101027342-G-C
• rs41319544
• NM_024652.6:c.2487G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-101027342-G-C
• chr15-101027342-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024652.6(LRRK1):​c.2487G>C​(p.Val829Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,728 control chromosomes in the GnomAD database, including 15,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1217 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14404 hom.)
• Consequence: LRRK1 NM_024652.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.204
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 15-101027342-G-C is Benign according to our data. Variant chr15-101027342-G-C is described in ClinVar as Benign. ClinVar VariationId is 1655883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.204 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK1	NM_024652.6	c.2487G>C	p.Val829Val	synonymous_variant	Exon 18 of 34	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8	c.2487G>C	p.Val829Val	synonymous_variant	Exon 18 of 34	5	NM_024652.6	ENSP00000373600.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18327 AN: 152118 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.114 AC: 28355 AN: 249140 AF XY: 0.116

Gnomad AFR exome AF: 0.0950

Gnomad AMR exome AF: 0.0766

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.0234

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.137 AC: 200063 AN: 1461492 Hom.: 14404 Cov.: 32 AF XY: 0.136 AC XY: 99079 AN XY: 727028

African (AFR) AF: 0.0889 AC: 2975 AN: 33480

American (AMR) AF: 0.0806 AC: 3606 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3722 AN: 26134

East Asian (EAS) AF: 0.0374 AC: 1485 AN: 39698

South Asian (SAS) AF: 0.0943 AC: 8132 AN: 86244

European-Finnish (FIN) AF: 0.107 AC: 5686 AN: 53248

Middle Eastern (MID) AF: 0.132 AC: 762 AN: 5764

European-Non Finnish (NFE) AF: 0.149 AC: 165780 AN: 1111822

Other (OTH) AF: 0.131 AC: 7915 AN: 60388

GnomAD4 genome AF: 0.120 AC: 18333 AN: 152236 Hom.: 1217 Cov.: 32 AF XY: 0.115 AC XY: 8529 AN XY: 74444

African (AFR) AF: 0.0964 AC: 4005 AN: 41526

American (AMR) AF: 0.107 AC: 1636 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5178

South Asian (SAS) AF: 0.0946 AC: 456 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10051 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.117 Hom.: 413

Bravo AF: 0.117

Asia WGS AF: 0.0940 AC: 328 AN: 3478

EpiCase AF: 0.151

EpiControl AF: 0.155

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LRRK1-related disorder Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.2
DANN	Benign	0.70
PhyloP100		-0.20
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41319544; hg19: chr15-101567547;