Variant rs4965778 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.3447A>G(p.Thr1149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,162 control chromosomes in the GnomAD database, including 140,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 12154 hom., cov: 33)

Exomes 𝑓: 0.41 ( 127960 hom. )

Consequence

LRRK1
NM_024652.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.42

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:

(HGNC:):

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=-0.9).

BP6

Variant 15-101051718-A-G is Benign according to our data. Variant chr15-101051718-A-G is described in ClinVar as [Benign]. Clinvar id is 1601184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 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.3447A>G	p.Thr1149=	synonymous_variant	24/34	ENST00000388948.8	NP_078928.3
LOC105371026	XR_001751726.2 linkuse as main transcript	n.1051-939T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8 linkuse as main transcript	c.3447A>G	p.Thr1149=	synonymous_variant	24/34	5	NM_024652.6	ENSP00000373600	P1	Q38SD2-1
LRRK1	ENST00000525284.5 linkuse as main transcript	c.*1380A>G		3_prime_UTR_variant, NMD_transcript_variant	23/33	1		ENSP00000433069
LRRK1	ENST00000531270.5 linkuse as main transcript	c.*1211A>G		3_prime_UTR_variant, NMD_transcript_variant	22/32	1		ENSP00000431668
	ENST00000559857.1 linkuse as main transcript	n.673-939T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55982

AN:

151974

Hom.:

12159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.369

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.458

AC:

113567

AN:

248140

Hom.:

28788

AF XY:

0.452

AC XY:

60887

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.807

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.511

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.447

GnomAD4 exome

AF:

0.409

AC:

597200

AN:

1461070

Hom.:

127960

Cov.:

AF XY:

0.410

AC XY:

297649

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.767

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.368

AC:

56000

AN:

152092

Hom.:

12154

Cov.:

AF XY:

0.382

AC XY:

28443

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.509

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.789

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.391

Hom.:

7386

Bravo

AF:

0.362

Asia WGS

AF:

0.543

AC:

1886

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.394

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

Oct 17, 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

-0.90

CADD

Benign

0.045

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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