11-27472179-C-G

Position:

• chr11-27472179-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018490.5(LGR4):​c.124G>C​(p.Asp42His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGR4 NM_018490.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65

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-AS1 (HGNC:40629): (LGR4 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR4	NM_018490.5	c.124G>C	p.Asp42His	missense_variant	1/18	ENST00000379214.9	NP_060960.2
LGR4-AS1	NR_131170.1	n.102+347C>G		intron_variant, non_coding_transcript_variant
LGR4	NM_001346432.2	c.124G>C	p.Asp42His	missense_variant	1/17		NP_001333361.1
LGR4-AS1	NR_131169.1	n.102+347C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR4	ENST00000379214.9	c.124G>C	p.Asp42His	missense_variant	1/18	1	NM_018490.5	ENSP00000368516	P1
LGR4-AS1	ENST00000529258.1	n.35+347C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.124G>C (p.D42H) alteration is located in exon 1 (coding exon 1) of the LGR4 gene. This alteration results from a G to C substitution at nucleotide position 124, causing the aspartic acid (D) at amino acid position 42 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;.;D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D;T;D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Uncertain	2.4	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.97	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.36
MutPred		0.60		Loss of disorder (P = 0.0688);Loss of disorder (P = 0.0688);Loss of disorder (P = 0.0688);
MVP		0.88
MPC		0.88
ClinPred		0.99	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.84
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27493726;