rs143988867

Variant names:

• chr12-71504649-C-G
• rs143988867
• NM_003667.4:c.248C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-71504649-C-G
• chr12-71504649-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003667.4(LGR5):​c.248C>G​(p.Pro83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P83L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LGR5 NM_003667.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 0 publications found

Genes affected

LGR5 (HGNC:4504): (leucine rich repeat containing G protein-coupled receptor 5) The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13881019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003667.4. 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
	LGR5	NM_003667.4	MANE Select	c.248C>G	p.Pro83Arg	missense	Exon 2 of 18	NP_003658.1	O75473-1
	LGR5	NM_001277226.2		c.248C>G	p.Pro83Arg	missense	Exon 2 of 17	NP_001264155.1	O75473-2
	LGR5	NM_001277227.2		c.248C>G	p.Pro83Arg	missense	Exon 2 of 17	NP_001264156.1	O75473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.248C>G	p.Pro83Arg	missense	Exon 2 of 18	ENSP00000266674.4	O75473-1
	LGR5	ENST00000540815.2	TSL:1	c.248C>G	p.Pro83Arg	missense	Exon 2 of 17	ENSP00000441035.2	O75473-2
	LGR5	ENST00000536515.5	TSL:1	c.248C>G	p.Pro83Arg	missense	Exon 2 of 17	ENSP00000443033.1	O75473-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251454 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.000061	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.65	N
PhyloP100		0.50
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.030
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.022	D
Polyphen		0.58	P
Vest4		0.19
MutPred		0.36		Gain of solvent accessibility (P = 0.0411)
MVP		0.88
MPC		0.054
ClinPred		0.23	T
GERP RS		2.9
Varity_R		0.23
gMVP		0.51
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143988867; hg19: chr12-71898429;