Genetic Variant LRRK1:c.1533-132G>T (chr15-101015194-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024652.6(LRRK1):c.1533-132G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRK1
NM_024652.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.11

Publications

11 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK1	NM_024652.6 link	c.1533-132G>T		intron_variant	Intron 11 of 33	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRK1	ENST00000388948.8 link	c.1533-132G>T	intron_variant	Intron 11 of 33	5	NM_024652.6	ENSP00000373600.3	Q38SD2-1
LRRK1	ENST00000525284.5 link	n.1533-132G>T	intron_variant	Intron 10 of 32	1		ENSP00000433069.1	E9PMK9
LRRK1	ENST00000531270.5 link	n.1533-132G>T	intron_variant	Intron 10 of 31	1		ENSP00000431668.1	E9PK39

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

528376

Hom.:

AF XY:

0.00

AC XY:

AN XY:

277312

African (AFR)

AF:

0.00

AC:

AN:

13950

American (AMR)

AF:

0.00

AC:

AN:

25224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15176

East Asian (EAS)

AF:

0.00

AC:

AN:

29896

South Asian (SAS)

AF:

0.00

AC:

AN:

50284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3792

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

317316

Other (OTH)

AF:

0.00

AC:

AN:

28552

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.025

(source)

DANN

Benign

0.41

PhyloP100

-6.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over