NM_003667.4:c.857+685C>T

Variant names:

• chr12-71562537-C-T
• rs1280605
• NM_003667.4:c.857+685C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003667.4(LGR5):​c.857+685C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,982 control chromosomes in the GnomAD database, including 39,163 homozygotes. 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 0.69 (39163 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 3 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]

LOC105369833 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

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.857+685C>T		intron	N/A	NP_003658.1	O75473-1
	LGR5	NM_001277226.2		c.785+2883C>T		intron	N/A	NP_001264155.1	O75473-2
	LGR5	NM_001277227.2		c.641+685C>T		intron	N/A	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.857+685C>T		intron	N/A	ENSP00000266674.4	O75473-1
	LGR5	ENST00000540815.2	TSL:1	c.785+2883C>T		intron	N/A	ENSP00000441035.2	O75473-2
	LGR5	ENST00000536515.5	TSL:1	c.641+685C>T		intron	N/A	ENSP00000443033.1	O75473-3

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104859 AN: 151864 Hom.: 39149 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104910 AN: 151982 Hom.: 39163 Cov.: 32 AF XY: 0.687 AC XY: 51070 AN XY: 74290

African (AFR) AF: 0.393 AC: 16253 AN: 41390

American (AMR) AF: 0.778 AC: 11883 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2743 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2873 AN: 5168

South Asian (SAS) AF: 0.594 AC: 2862 AN: 4816

European-Finnish (FIN) AF: 0.803 AC: 8467 AN: 10546

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57327 AN: 68008

Other (OTH) AF: 0.712 AC: 1503 AN: 2112

Alfa AF: 0.775 Hom.: 86238

Bravo AF: 0.676

Asia WGS AF: 0.552 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.21
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs1280605; hg19: chr12-71956317;