LGR4 p.Arg126Arg

Variant names:

• chr11-27391116-C-C
• NM_018490.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr11-27391117--
• chr11-27391117-T-A
• chr11-27391117-T-G
• chr11-27391117-T-C
• chr11-27391119-G-T
• chr11-27391117-TCG-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018490.5(LGR4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGR4 NM_018490.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 0 publications found

Genes affected

LGR4 (HGNC:13299): (leucine rich repeat containing G protein-coupled receptor 4) The protein encoded by this gene is a G-protein coupled receptor that binds R-spondins and activates the Wnt signaling pathway. This Wnt signaling pathway activation is necessary for proper development of many organs of the body. [provided by RefSeq, Oct 2016]

LGR4 Gene-Disease associations (from GenCC):

• delayed puberty, self-limited

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018490.5. 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
	LGR4	NM_018490.5	MANE Select	c.		exon_region	Exon 4 of 18	NP_060960.2	Q9BXB1-1
	LGR4	NM_001346432.2		c.		exon_region	Exon 3 of 17	NP_001333361.1	Q9BXB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR4	ENST00000379214.9	TSL:1 MANE Select	c.		exon_region	Exon 4 of 18	ENSP00000368516.4	Q9BXB1-1
	LGR4	ENST00000389858.4	TSL:1	c.		exon_region	Exon 3 of 17	ENSP00000374508.4	Q9BXB1-2
	LGR4	ENST00000937760.1		c.		exon_region	Exon 4 of 17	ENSP00000607819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-27412663;