rs2412000

Variant names:

• chr15-100989389-G-A
• rs2412000
• NM_024652.6:c.753G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-100989389-G-A
• chr15-100989389-G-C

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.753G>A​(p.Pro251Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 1,613,942 control chromosomes in the GnomAD database, including 6,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2430 hom., cov: 33)
  • Exomes 𝑓: 0.058 (4147 hom.)
• Consequence: LRRK1 NM_024652.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.99
• Publications: 6 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=-0.81).
• BP6: Variant 15-100989389-G-A is Benign according to our data. Variant chr15-100989389-G-A is described in CliVar as Benign. Clinvar id is 1636917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-100989389-G-A is described in CliVar as Benign. Clinvar id is 1636917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-100989389-G-A is described in CliVar as Benign. Clinvar id is 1636917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK1	NM_024652.6	c.753G>A	p.Pro251Pro	synonymous_variant	Exon 6 of 34	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8	c.753G>A	p.Pro251Pro	synonymous_variant	Exon 6 of 34	5	NM_024652.6	ENSP00000373600.3
LRRK1	ENST00000532029.6	c.753G>A	p.Pro251Pro	synonymous_variant	Exon 6 of 6	1		ENSP00000433268.2
LRRK1	ENST00000525284.5	n.753G>A		non_coding_transcript_exon_variant	Exon 5 of 33	1		ENSP00000433069.1
LRRK1	ENST00000531270.5	n.753G>A		non_coding_transcript_exon_variant	Exon 5 of 32	1		ENSP00000431668.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19305 AN: 152112 Hom.: 2423 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0768

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.0645 AC: 16091 AN: 249476 AF XY: 0.0615

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.0453

Gnomad ASJ exome AF: 0.0715

Gnomad EAS exome AF: 0.00578

Gnomad FIN exome AF: 0.0265

Gnomad NFE exome AF: 0.0486

Gnomad OTH exome AF: 0.0589

GnomAD4 exome AF: 0.0585 AC: 85494 AN: 1461712 Hom.: 4147 Cov.: 32 AF XY: 0.0580 AC XY: 42142 AN XY: 727158

African (AFR) AF: 0.344 AC: 11520 AN: 33472

American (AMR) AF: 0.0501 AC: 2239 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 1786 AN: 26134

East Asian (EAS) AF: 0.0109 AC: 431 AN: 39700

South Asian (SAS) AF: 0.0612 AC: 5276 AN: 86248

European-Finnish (FIN) AF: 0.0280 AC: 1493 AN: 53412

Middle Eastern (MID) AF: 0.0900 AC: 514 AN: 5714

European-Non Finnish (NFE) AF: 0.0519 AC: 57751 AN: 1111918

Other (OTH) AF: 0.0742 AC: 4484 AN: 60392

GnomAD4 genome AF: 0.127 AC: 19357 AN: 152230 Hom.: 2430 Cov.: 33 AF XY: 0.123 AC XY: 9132 AN XY: 74436

African (AFR) AF: 0.329 AC: 13652 AN: 41496

American (AMR) AF: 0.0766 AC: 1172 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3470

East Asian (EAS) AF: 0.00809 AC: 42 AN: 5192

South Asian (SAS) AF: 0.0530 AC: 256 AN: 4830

European-Finnish (FIN) AF: 0.0294 AC: 312 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0503 AC: 3424 AN: 68020

Other (OTH) AF: 0.113 AC: 240 AN: 2116

Alfa AF: 0.0808 Hom.: 1552

Bravo AF: 0.140

Asia WGS AF: 0.0660 AC: 231 AN: 3478

EpiCase AF: 0.0538

EpiControl AF: 0.0540

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

LRRK1-related disorder Benign:1

Apr 09, 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	-0.81
CADD	Benign	0.038
DANN	Benign	0.44
PhyloP100		-2.0
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: rs2412000; hg19: chr15-101529594;