rs7975693

Variant names:

• chr12-40194876-C-T
• rs7975693
• ENST00000412812.2:n.238-4482G>A

Variant summary

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

The ENST00000412812.2(LRRK2-DT):​n.238-4482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,246 control chromosomes in the GnomAD database, including 1,065 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 0.11 (1065 hom., cov: 32)
• Consequence: LRRK2-DT ENST00000412812.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 3 publications found

Genes affected

LRRK2-DT (HGNC:40848): (LRRK2 divergent transcript)

LINC02471 (HGNC:53410): (long intergenic non-protein coding RNA 2471)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412812.2. 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
	LRRK2-DT	NR_186756.1		n.165-4482G>A		intron	N/A
	LRRK2-DT	NR_186757.1		n.165-27509G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK2-DT	ENST00000412812.2	TSL:4	n.238-4482G>A		intron	N/A
	LINC02471	ENST00000641941.1		n.232-3330C>T		intron	N/A
	LINC02471	ENST00000783096.1		n.156-8576C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16333 AN: 152128 Hom.: 1064 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.107 AC: 16329 AN: 152246 Hom.: 1065 Cov.: 32 AF XY: 0.106 AC XY: 7898 AN XY: 74436

African (AFR) AF: 0.0404 AC: 1679 AN: 41554

American (AMR) AF: 0.111 AC: 1699 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.189 AC: 978 AN: 5182

South Asian (SAS) AF: 0.105 AC: 505 AN: 4826

European-Finnish (FIN) AF: 0.0820 AC: 869 AN: 10600

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9540 AN: 68010

Other (OTH) AF: 0.133 AC: 280 AN: 2108

Alfa AF: 0.0970 Hom.: 420

Bravo AF: 0.108

Asia WGS AF: 0.133 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7975693; hg19: chr12-40588678;