NM_003667.4:c.601A>C

Variant names:

• chr12-71553245-A-C
• rs768780796
• NM_003667.4:c.601A>C

Variant summary

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

The NM_003667.4(LGR5):​c.601A>C​(p.Ile201Leu) variant causes a missense change. 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: 31)
• Consequence: LGR5 NM_003667.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.37

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]

LOC105369833 (HGNC:):

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 rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.601A>C	p.Ile201Leu	missense_variant	Exon 5 of 18	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.601A>C	p.Ile201Leu	missense_variant	Exon 5 of 18	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.601A>C	p.Ile201Leu	missense_variant	Exon 5 of 17	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.429-3374A>C		intron_variant	Intron 4 of 16	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.698A>C		non_coding_transcript_exon_variant	Exon 5 of 20	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251106 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135694

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.97	D;P
Vest4		0.69
MutPred		0.50		Gain of catalytic residue at D203 (P = 0);Gain of catalytic residue at D203 (P = 0);
MVP		0.96
MPC		0.085
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.65
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs768780796; hg19: chr12-71947025;