Variant 15-101066056-C-T 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.5619C>T(p.Thr1873=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 1,614,034 control chromosomes in the GnomAD database, including 8,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 955 hom., cov: 33)

Exomes 𝑓: 0.084 ( 7802 hom. )

Consequence

LRRK1
NM_024652.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.26

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:

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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 15-101066056-C-T is Benign according to our data. Variant chr15-101066056-C-T is described in ClinVar as [Benign]. Clinvar id is 1574345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 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.5619C>T	p.Thr1873=	synonymous_variant	32/34	ENST00000388948.8
LOC105371026	XR_001751726.2 linkuse as main transcript	n.1051-15277G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK1	ENST00000388948.8 linkuse as main transcript	c.5619C>T	p.Thr1873=	synonymous_variant	32/34	5	NM_024652.6	P1	Q38SD2-1
	ENST00000559857.1 linkuse as main transcript	n.369-392G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12933

AN:

152088

Hom.:

957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0798

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0698

Gnomad OTH

AF:

0.0943

GnomAD3 exomes

AF:

0.126

AC:

31297

AN:

248732

Hom.:

3183

AF XY:

0.119

AC XY:

16091

AN XY:

135028

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.0758

Gnomad EAS exome

AF:

0.348

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.0704

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0841

AC:

123007

AN:

1461826

Hom.:

7802

Cov.:

AF XY:

0.0842

AC XY:

61220

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.251

Gnomad4 ASJ exome

AF:

0.0798

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.0657

Gnomad4 OTH exome

AF:

0.0947

GnomAD4 genome

AF:

0.0850

AC:

12932

AN:

152208

Hom.:

955

Cov.:

AF XY:

0.0921

AC XY:

6855

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0798

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.0698

Gnomad4 OTH

AF:

0.0942

Alfa

AF:

0.0775

Hom.:

837

Bravo

AF:

0.0873

Asia WGS

AF:

0.219

AC:

761

AN:

3478

EpiCase

AF:

0.0655

EpiControl

AF:

0.0673

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

Feb 21, 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

-0.90

CADD

Benign

0.20

DANN

Benign

0.77

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