Variant chr12-40315611-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198578.4(LRRK2):c.4827+311T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,798 control chromosomes in the GnomAD database, including 37,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 37320 hom., cov: 31)

Consequence

LRRK2
NM_198578.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

LRRK2 (HGNC:18618): (leucine rich repeat kinase 2) This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008]

LRRK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRK2	NM_198578.4 link	c.4827+311T>A		intron_variant		ENST00000298910.12	NP_940980.4	Q5S007Q17RV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12 link	c.4827+311T>A		intron_variant		1	NM_198578.4	ENSP00000298910.7		Q5S007

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105879

AN:

151680

Hom.:

37285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.769

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.781

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.674

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.698

AC:

105972

AN:

151798

Hom.:

37320

Cov.:

AF XY:

0.704

AC XY:

52245

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.769

Gnomad4 AMR

AF:

0.713

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.719

Gnomad4 FIN

AF:

0.781

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.670

Alfa

AF:

0.698

Hom.:

4603

Bravo

AF:

0.691

Asia WGS

AF:

0.633

AC:

2200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.2

DANN

Benign

0.37

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over