Variant chr15-101021111-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.1668C>T(p.Asn556=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,058 control chromosomes in the GnomAD database, including 2,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 1119 hom., cov: 31)

Exomes 𝑓: 0.0074 ( 1012 hom. )

Consequence

LRRK1
NM_024652.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.72

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:

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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=-0.7).

BP6

Variant 15-101021111-C-T is Benign according to our data. Variant chr15-101021111-C-T is described in ClinVar as [Benign]. Clinvar id is 1623610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.1668C>T	p.Asn556=	synonymous_variant	13/34	ENST00000388948.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK1	ENST00000388948.8 linkuse as main transcript	c.1668C>T	p.Asn556=	synonymous_variant	13/34	5	NM_024652.6	P1	Q38SD2-1
LRRK1	ENST00000525284.5 linkuse as main transcript	c.1668C>T	p.Asn556=	synonymous_variant, NMD_transcript_variant	12/33	1
LRRK1	ENST00000531270.5 linkuse as main transcript	c.1668C>T	p.Asn556=	synonymous_variant, NMD_transcript_variant	12/32	1

Frequencies

GnomAD3 genomes

AF:

0.0667

AC:

10144

AN:

152110

Hom.:

1114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0257

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0175

AC:

4361

AN:

249582

Hom.:

451

AF XY:

0.0132

AC XY:

1794

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.00979

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00891

GnomAD4 exome

AF:

0.00739

AC:

10803

AN:

1461830

Hom.:

1012

Cov.:

AF XY:

0.00640

AC XY:

4651

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.000700

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0668

AC:

10172

AN:

152228

Hom.:

1119

Cov.:

AF XY:

0.0651

AC XY:

4845

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.0256

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.0517

Alfa

AF:

0.0313

Hom.:

235

Bravo

AF:

0.0758

Asia WGS

AF:

0.0120

AC:

AN:

3478

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

Dec 23, 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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.8

DANN

Benign

0.57

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