rs2304274

Variant names:

• chr12-71556969-G-A
• rs2304274
• NM_003667.4:c.716+279G>A

Variant summary

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

The NM_003667.4(LGR5):​c.716+279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,204 control chromosomes in the GnomAD database, including 1,438 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 (1438 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• 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]

LOC105369833 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.716+279G>A		intron_variant	Intron 6 of 17	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.716+279G>A		intron_variant	Intron 6 of 17	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.716+279G>A		intron_variant	Intron 6 of 16	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.500+279G>A		intron_variant	Intron 5 of 16	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.813+279G>A		intron_variant	Intron 6 of 19	2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17961 AN: 152086 Hom.: 1429 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.118 AC: 17994 AN: 152204 Hom.: 1438 Cov.: 32 AF XY: 0.123 AC XY: 9115 AN XY: 74406

African (AFR) AF: 0.136 AC: 5655 AN: 41520

American (AMR) AF: 0.134 AC: 2054 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1994 AN: 5162

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4824

European-Finnish (FIN) AF: 0.0838 AC: 888 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0774 AC: 5264 AN: 68024

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.0972 Hom.: 480

Bravo AF: 0.121

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.59
PhyloP100		0.14
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: rs2304274; hg19: chr12-71950749;