rs7307225

Variant names:

• chr12-71504578-T-C
• rs7307225
• NM_003667.4:c.213-36T>C

Variant summary

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

The NM_003667.4(LGR5):​c.213-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,551,822 control chromosomes in the GnomAD database, including 9,015 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 0.093 (709 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8306 hom.)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.213-36T>C		intron_variant	Intron 1 of 17	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.213-36T>C		intron_variant	Intron 1 of 17	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.213-36T>C		intron_variant	Intron 1 of 16	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.213-36T>C		intron_variant	Intron 1 of 16	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.310-36T>C		intron_variant	Intron 1 of 19	2

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14212 AN: 152136 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0928

GnomAD2 exomes AF: 0.0875 AC: 21976 AN: 251190 AF XY: 0.0903

Gnomad AFR exome AF: 0.0870

Gnomad AMR exome AF: 0.0492

Gnomad ASJ exome AF: 0.0710

Gnomad EAS exome AF: 0.00147

Gnomad FIN exome AF: 0.0932

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0835

GnomAD4 exome AF: 0.105 AC: 147252 AN: 1399568 Hom.: 8306 Cov.: 25 AF XY: 0.105 AC XY: 73817 AN XY: 700084

African (AFR) AF: 0.0826 AC: 2659 AN: 32192

American (AMR) AF: 0.0504 AC: 2249 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1837 AN: 25784

East Asian (EAS) AF: 0.000913 AC: 36 AN: 39412

South Asian (SAS) AF: 0.108 AC: 9200 AN: 84964

European-Finnish (FIN) AF: 0.0924 AC: 4935 AN: 53384

Middle Eastern (MID) AF: 0.0811 AC: 458 AN: 5648

European-Non Finnish (NFE) AF: 0.114 AC: 120073 AN: 1055288

Other (OTH) AF: 0.0996 AC: 5805 AN: 58270

GnomAD4 genome AF: 0.0934 AC: 14213 AN: 152254 Hom.: 709 Cov.: 32 AF XY: 0.0920 AC XY: 6852 AN XY: 74440

African (AFR) AF: 0.0869 AC: 3609 AN: 41532

American (AMR) AF: 0.0715 AC: 1093 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 222 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.0948 AC: 458 AN: 4832

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10604

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.110 AC: 7476 AN: 68022

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.101 Hom.: 1043

Bravo AF: 0.0889

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.35
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs7307225; hg19: chr12-71898358;