rs2034809

Variant names:

• chr15-101015194-G-A
• rs2034809
• NM_024652.6:c.1533-132G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-101015194-G-A
• chr15-101015194-G-C
• chr15-101015194-G-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.1533-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 679,346 control chromosomes in the GnomAD database, including 90,068 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 0.47 (17789 hom., cov: 32)
  • Exomes 𝑓: 0.52 (72279 hom.)
• Consequence: LRRK1 NM_024652.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.11
• Publications: 11 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71447 AN: 151938 Hom.: 17779 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.515 AC: 271699 AN: 527290 Hom.: 72279 AF XY: 0.513 AC XY: 142103 AN XY: 276738

African (AFR) AF: 0.332 AC: 4623 AN: 13914

American (AMR) AF: 0.626 AC: 15753 AN: 25170

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 8725 AN: 15144

East Asian (EAS) AF: 0.774 AC: 23095 AN: 29850

South Asian (SAS) AF: 0.488 AC: 24515 AN: 50208

European-Finnish (FIN) AF: 0.532 AC: 23452 AN: 44094

Middle Eastern (MID) AF: 0.596 AC: 2259 AN: 3790

European-Non Finnish (NFE) AF: 0.488 AC: 154544 AN: 316622

Other (OTH) AF: 0.517 AC: 14733 AN: 28498

GnomAD4 genome AF: 0.470 AC: 71496 AN: 152056 Hom.: 17789 Cov.: 32 AF XY: 0.477 AC XY: 35420 AN XY: 74328

African (AFR) AF: 0.326 AC: 13531 AN: 41498

American (AMR) AF: 0.575 AC: 8785 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2016 AN: 3468

East Asian (EAS) AF: 0.785 AC: 4055 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2422 AN: 4810

European-Finnish (FIN) AF: 0.544 AC: 5748 AN: 10560

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33186 AN: 67962

Other (OTH) AF: 0.513 AC: 1083 AN: 2112

Alfa AF: 0.489 Hom.: 31940

Bravo AF: 0.469

Asia WGS AF: 0.605 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.040
DANN	Benign	0.59
PhyloP100		-6.1
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: rs2034809; hg19: chr15-101555399;