rs7307225

Positions:

• chr12-71504578-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LGR5	NM_003667.4	c.213-36T>C		intron_variant		ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.213-36T>C		intron_variant		1	NM_003667.4	ENSP00000266674	P1
LGR5	ENST00000536515.5	c.213-36T>C		intron_variant		1		ENSP00000443033
LGR5	ENST00000540815.2	c.213-36T>C		intron_variant		1		ENSP00000441035
LGR5	ENST00000550851.5	n.310-36T>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0875 AC: 21976 AN: 251190 Hom.: 1125 AF XY: 0.0903 AC XY: 12263 AN XY: 135738

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 SAS exome AF: 0.107

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

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.000913

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0924

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.0996

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

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.100 Hom.: 873

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7307225; hg19: chr12-71898358;