Variant rs41319544 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024652.6(LRRK1):c.2487G>C(p.Val829=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.204

Variant links:

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]

LRRK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
LRRK1	NM_024652.6 linkuse as main transcript	c.2487G>C	p.Val829=	synonymous_variant	18/34	ENST00000388948.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK1	ENST00000388948.8 linkuse as main transcript	c.2487G>C	p.Val829=	synonymous_variant	18/34	5	NM_024652.6	P1	Q38SD2-1
LRRK1	ENST00000525284.5 linkuse as main transcript	c.*420G>C		3_prime_UTR_variant, NMD_transcript_variant	17/33	1
LRRK1	ENST00000531270.5 linkuse as main transcript	c.*415G>C		3_prime_UTR_variant, NMD_transcript_variant	17/32	1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18327

AN:

152118

Hom.:

1217

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.114

AC:

28355

AN:

249140

Hom.:

1864

AF XY:

0.116

AC XY:

15665

AN XY:

135236

show subpopulations

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 SAS exome

AF:

0.0955

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.:

AF XY:

0.136

AC XY:

99079

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0889

Gnomad4 AMR exome

AF:

0.0806

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0374

Gnomad4 SAS exome

AF:

0.0943

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.120

AC:

18333

AN:

152236

Hom.:

1217

Cov.:

AF XY:

0.115

AC XY:

8529

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0964

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0278

Gnomad4 SAS

AF:

0.0946

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.127

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

LRRK1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.2

DANN

Benign

0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over