15-101015087-C-T

Variant names:

• chr15-101015087-C-T
• rs2412004
• NM_024652.6:c.1533-239C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000388948.8(LRRK1):​c.1533-239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,024 control chromosomes in the GnomAD database, including 19,411 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 0.48 (19411 hom., cov: 32)
• Consequence: LRRK1 ENST00000388948.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000388948.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	NM_024652.6	MANE Select	c.1533-239C>T		intron	N/A	NP_078928.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	ENST00000388948.8	TSL:5 MANE Select	c.1533-239C>T		intron	N/A	ENSP00000373600.3
	LRRK1	ENST00000525284.5	TSL:1	n.1533-239C>T		intron	N/A	ENSP00000433069.1
	LRRK1	ENST00000531270.5	TSL:1	n.1533-239C>T		intron	N/A	ENSP00000431668.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72464 AN: 151906 Hom.: 19419 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.477 AC: 72454 AN: 152024 Hom.: 19411 Cov.: 32 AF XY: 0.482 AC XY: 35819 AN XY: 74304

African (AFR) AF: 0.214 AC: 8869 AN: 41494

American (AMR) AF: 0.537 AC: 8196 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3466

East Asian (EAS) AF: 0.539 AC: 2777 AN: 5156

South Asian (SAS) AF: 0.576 AC: 2773 AN: 4816

European-Finnish (FIN) AF: 0.614 AC: 6494 AN: 10582

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39964 AN: 67930

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.562 Hom.: 14193

Bravo AF: 0.458

Asia WGS AF: 0.538 AC: 1871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.68
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2412004; hg19: chr15-101555292;