rs79665807

chr12-71501437-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003667.4(LGR5):c.213-3177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 152,326 control chromosomes in the GnomAD database, including 16 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 0.012 (16 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1860/152326) while in subpopulation AFR AF= 0.0165 (686/41566). AF 95% confidence interval is 0.0155. There are 16 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4	c.213-3177T>C		intron_variant		ENST00000266674.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGR5	ENST00000266674.10	c.213-3177T>C		intron_variant		1	NM_003667.4	P1
LGR5	ENST00000536515.5	c.213-3177T>C		intron_variant		1
LGR5	ENST00000540815.2	c.213-3177T>C		intron_variant		1
LGR5	ENST00000550851.5	n.310-3177T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1855 AN: 152208 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0122 AC: 1860 AN: 152326 Hom.: 16 Cov.: 32 AF XY: 0.0118 AC XY: 877 AN XY: 74498

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0113 Hom.: 2

Bravo AF: 0.0133

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.36
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs79665807; hg19: chr12-71895217;