rs56215707

Variant names:

• chr15-101021111-C-T
• rs56215707
• NM_024652.6:c.1668C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-101021111-C-T
• chr15-101021111-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024652.6(LRRK1):​c.1668C>T​(p.Asn556Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,058 control chromosomes in the GnomAD database, including 2,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (1119 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (1012 hom.)
• Consequence: LRRK1 NM_024652.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.72
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 15-101021111-C-T is Benign according to our data. Variant chr15-101021111-C-T is described in ClinVar as Benign. ClinVar VariationId is 1623610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024652.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	NM_024652.6	MANE Select	c.1668C>T	p.Asn556Asn	synonymous	Exon 13 of 34	NP_078928.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRK1	ENST00000388948.8	TSL:5 MANE Select	c.1668C>T	p.Asn556Asn	synonymous	Exon 13 of 34	ENSP00000373600.3	Q38SD2-1
	LRRK1	ENST00000525284.5	TSL:1	n.1668C>T		non_coding_transcript_exon	Exon 12 of 33	ENSP00000433069.1	E9PMK9
	LRRK1	ENST00000531270.5	TSL:1	n.1668C>T		non_coding_transcript_exon	Exon 12 of 32	ENSP00000431668.1	E9PK39

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10144 AN: 152110 Hom.: 1114 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0522

GnomAD2 exomes AF: 0.0175 AC: 4361 AN: 249582 AF XY: 0.0132

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.00979

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00891

GnomAD4 exome AF: 0.00739 AC: 10803 AN: 1461830 Hom.: 1012 Cov.: 31 AF XY: 0.00640 AC XY: 4651 AN XY: 727232

African (AFR) AF: 0.240 AC: 8023 AN: 33480

American (AMR) AF: 0.0115 AC: 515 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 415 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53420

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.000700 AC: 778 AN: 1111952

Other (OTH) AF: 0.0155 AC: 935 AN: 60396

GnomAD4 genome AF: 0.0668 AC: 10172 AN: 152228 Hom.: 1119 Cov.: 31 AF XY: 0.0651 AC XY: 4845 AN XY: 74438

African (AFR) AF: 0.230 AC: 9538 AN: 41486

American (AMR) AF: 0.0256 AC: 392 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68026

Other (OTH) AF: 0.0517 AC: 109 AN: 2110

Alfa AF: 0.0320 Hom.: 323

Bravo AF: 0.0758

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	LRRK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.8
DANN	Benign	0.57
PhyloP100		-1.7
Mutation Taster		=99/1	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: rs56215707; hg19: chr15-101561316;