Variant 15-100988807-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024652.6(LRRK1):c.607A>G(p.Lys203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,597,388 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 159 hom. )

Consequence

LRRK1
NM_024652.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.41

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044516325).

BP6

Variant 15-100988807-A-G is Benign according to our data. Variant chr15-100988807-A-G is described in ClinVar as [Benign]. Clinvar id is 1537753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0726 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.607A>G	p.Lys203Glu	missense_variant	5/34	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.607A>G	p.Lys203Glu	missense_variant	5/34	5	NM_024652.6	ENSP00000373600	P1	Q38SD2-1
LRRK1	ENST00000532029.6 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant	5/6	1		ENSP00000433268		Q38SD2-2
LRRK1	ENST00000525284.5 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant, NMD_transcript_variant	4/33	1		ENSP00000433069
LRRK1	ENST00000531270.5 linkuse as main transcript	c.607A>G	p.Lys203Glu	missense_variant, NMD_transcript_variant	4/32	1		ENSP00000431668

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

430

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0420

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00487

AC:

1171

AN:

240406

Hom.:

AF XY:

0.00485

AC XY:

630

AN XY:

129946

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0351

Gnomad SAS exome

AF:

0.00591

Gnomad FIN exome

AF:

0.00909

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00550

GnomAD4 exome

AF:

0.00326

AC:

4718

AN:

1445054

Hom.:

159

Cov.:

AF XY:

0.00342

AC XY:

2447

AN XY:

715986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0749

Gnomad4 SAS exome

AF:

0.00655

Gnomad4 FIN exome

AF:

0.00921

Gnomad4 NFE exome

AF:

0.000457

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00281

AC:

428

AN:

152334

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0419

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.00206

ESP6500AA

AF:

0.000728

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.00507

AC:

613

Asia WGS

AF:

0.0170

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

LRRK1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 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

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.086

Eigen_PC

Benign

0.090

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.82

D;D;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.042

Sift

Benign

0.043

D;T

Sift4G

Benign

0.068

T;D

Polyphen

0.011

B;B

Vest4

0.43

MVP

0.83

MPC

0.58

ClinPred

0.020

GERP RS

5.2

Varity_R

0.13

gMVP

0.58

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