15-101018357-G-T

Variant names:

• chr15-101018357-G-T
• rs930847
• NM_024652.6:c.1610-2696G>T

Variant summary

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

The NM_024652.6(LRRK1):​c.1610-2696G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,048 control chromosomes in the GnomAD database, including 37,305 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 0.68 (37305 hom., cov: 32)
• Consequence: LRRK1 NM_024652.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 23 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK1	NM_024652.6	c.1610-2696G>T		intron_variant	Intron 12 of 33	ENST00000388948.8	NP_078928.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK1	ENST00000388948.8	c.1610-2696G>T		intron_variant	Intron 12 of 33	5	NM_024652.6	ENSP00000373600.3
LRRK1	ENST00000525284.5	n.1610-2696G>T		intron_variant	Intron 11 of 32	1		ENSP00000433069.1
LRRK1	ENST00000531270.5	n.1610-2696G>T		intron_variant	Intron 11 of 31	1		ENSP00000431668.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103039 AN: 151930 Hom.: 37296 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.678 AC: 103079 AN: 152048 Hom.: 37305 Cov.: 32 AF XY: 0.689 AC XY: 51175 AN XY: 74326

African (AFR) AF: 0.398 AC: 16473 AN: 41400

American (AMR) AF: 0.781 AC: 11940 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2857 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4108 AN: 5170

South Asian (SAS) AF: 0.850 AC: 4098 AN: 4820

European-Finnish (FIN) AF: 0.819 AC: 8672 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52412 AN: 68002

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.739 Hom.: 126854

Bravo AF: 0.662

Asia WGS AF: 0.726 AC: 2526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		0.15
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: rs930847; hg19: chr15-101558562;