Variant rs2412000 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.753G>A(p.Pro251=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.99

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=-0.81).

BP6

Variant 15-100989389-G-A is Benign according to our data. Variant chr15-100989389-G-A is described in ClinVar 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/exons	MANE	Protein	UniProt
LRRK1	NM_024652.6 linkuse as main transcript	c.753G>A	p.Pro251=	synonymous_variant	6/34	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8 linkuse as main transcript	c.753G>A	p.Pro251=	synonymous_variant	6/34	5	NM_024652.6	ENSP00000373600	P1	Q38SD2-1
LRRK1	ENST00000532029.6 linkuse as main transcript	c.753G>A	p.Pro251=	synonymous_variant	6/6	1		ENSP00000433268		Q38SD2-2
LRRK1	ENST00000525284.5 linkuse as main transcript	c.753G>A	p.Pro251=	synonymous_variant, NMD_transcript_variant	5/33	1		ENSP00000433069
LRRK1	ENST00000531270.5 linkuse as main transcript	c.753G>A	p.Pro251=	synonymous_variant, NMD_transcript_variant	5/32	1		ENSP00000431668

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19305

AN:

152112

Hom.:

2423

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0645

AC:

16091

AN:

249476

Hom.:

1190

AF XY:

0.0615

AC XY:

8318

AN XY:

135340

show subpopulations

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 SAS exome

AF:

0.0641

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.:

AF XY:

0.0580

AC XY:

42142

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.0501

Gnomad4 ASJ exome

AF:

0.0683

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.0612

Gnomad4 FIN exome

AF:

0.0280

Gnomad4 NFE exome

AF:

0.0519

Gnomad4 OTH exome

AF:

0.0742

GnomAD4 genome

AF:

0.127

AC:

19357

AN:

152230

Hom.:

2430

Cov.:

AF XY:

0.123

AC XY:

9132

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.0766

Gnomad4 ASJ

AF:

0.0640

Gnomad4 EAS

AF:

0.00809

Gnomad4 SAS

AF:

0.0530

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0503

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0725

Hom.:

973

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

LRRK1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.038

DANN

Benign

0.44

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

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