rs2046932

Positions:

• chr12-40186638-G-A
• chr12-40186638-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412812.1(LRRK2-DT):​n.411-455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 152,212 control chromosomes in the GnomAD database, including 270 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 0.050 (270 hom., cov: 32)
• Consequence: LRRK2-DT ENST00000412812.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

Genes affected

LRRK2-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRK2-DT	NR_186756.1	n.430-1017C>T		intron_variant
LRRK2-DT	NR_186757.1	n.165-19271C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRK2-DT	ENST00000412812.1	n.411-455C>T		intron_variant		4
LINC02471	ENST00000641941.1	n.232-11568G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7610 AN: 152094 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.0481

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0500 AC: 7613 AN: 152212 Hom.: 270 Cov.: 32 AF XY: 0.0493 AC XY: 3666 AN XY: 74428

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0598 Hom.: 183

Bravo AF: 0.0474

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.4
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2046932; hg19: chr12-40580440;