chr12-71581035-A-G

Variant names:

• chr12-71581035-A-G
• rs10879303
• NM_003667.4:c.1552+612A>G

Variant summary

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

The NM_003667.4(LGR5):​c.1552+612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,198 control chromosomes in the GnomAD database, including 1,301 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 0.12 (1301 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75
• Publications: 1 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]

LOC124902963 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	NM_003667.4	MANE Select	c.1552+612A>G		intron	N/A	NP_003658.1
	LGR5	NM_001277226.2		c.1480+612A>G		intron	N/A	NP_001264155.1
	LGR5	NM_001277227.2		c.1336+612A>G		intron	N/A	NP_001264156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.1552+612A>G		intron	N/A	ENSP00000266674.4
	LGR5	ENST00000540815.2	TSL:1	c.1480+612A>G		intron	N/A	ENSP00000441035.2
	LGR5	ENST00000536515.5	TSL:1	c.1336+612A>G		intron	N/A	ENSP00000443033.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17797 AN: 152080 Hom.: 1300 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.117 AC: 17820 AN: 152198 Hom.: 1301 Cov.: 32 AF XY: 0.117 AC XY: 8734 AN XY: 74432

African (AFR) AF: 0.200 AC: 8317 AN: 41528

American (AMR) AF: 0.0906 AC: 1385 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5180

South Asian (SAS) AF: 0.125 AC: 604 AN: 4818

European-Finnish (FIN) AF: 0.0982 AC: 1041 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5853 AN: 67998

Other (OTH) AF: 0.102 AC: 216 AN: 2110

Alfa AF: 0.113 Hom.: 162

Bravo AF: 0.118

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0020
DANN	Benign	0.52
PhyloP100		-4.7
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: rs10879303; hg19: chr12-71974815;