chr12-71583995-G-A

Variant names:

• chr12-71583995-G-A
• rs61737423
• NM_003667.4:c.1985G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003667.4(LGR5):​c.1985G>A​(p.Arg662His) variant causes a missense change. The variant allele was found at a frequency of 0.000217 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: LGR5 NM_003667.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.77
• Publications: 5 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]

ENSG00000288530 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019456655).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	NM_003667.4	MANE Select	c.1985G>A	p.Arg662His	missense	Exon 18 of 18	NP_003658.1
	LGR5	NM_001277226.2		c.1913G>A	p.Arg638His	missense	Exon 17 of 17	NP_001264155.1
	LGR5	NM_001277227.2		c.1769G>A	p.Arg590His	missense	Exon 17 of 17	NP_001264156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.1985G>A	p.Arg662His	missense	Exon 18 of 18	ENSP00000266674.4
	LGR5	ENST00000540815.2	TSL:1	c.1913G>A	p.Arg638His	missense	Exon 17 of 17	ENSP00000441035.2
	LGR5	ENST00000536515.5	TSL:1	c.1769G>A	p.Arg590His	missense	Exon 17 of 17	ENSP00000443033.1

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000306 AC: 77 AN: 251442 AF XY: 0.000258

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000156 AC: 228 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 727246

African (AFR) AF: 0.00248 AC: 83 AN: 33478

American (AMR) AF: 0.000402 AC: 18 AN: 44724

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1112010

Other (OTH) AF: 0.000182 AC: 11 AN: 60396

GnomAD4 genome AF: 0.000808 AC: 123 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000766 AC XY: 57 AN XY: 74456

African (AFR) AF: 0.00277 AC: 115 AN: 41544

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000344 Hom.: 0

Bravo AF: 0.000903

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000387 AC: 47

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	0.12
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.019	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.75
Sift	Benign	0.082	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.48
MVP		0.98
MPC		0.37
ClinPred		0.16	T
GERP RS		6.0
Varity_R		0.22
gMVP		0.89
Mutation Taster		=56/44	polymorphism

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: rs61737423; hg19: chr12-71977775; COSMIC: COSV57008309; COSMIC: COSV57008309;