chr12-71562233-A-G

Variant names:

• chr12-71562233-A-G
• rs724201
• NM_003667.4:c.857+381A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003667.4(LGR5):​c.857+381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 152,048 control chromosomes in the GnomAD database, including 22,101 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 0.49 (22101 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.857+381A>G		intron_variant	Intron 8 of 17	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.857+381A>G		intron_variant	Intron 8 of 17	1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.785+2579A>G		intron_variant	Intron 7 of 16	1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.641+381A>G		intron_variant	Intron 7 of 16	1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.954+381A>G		intron_variant	Intron 8 of 19	2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74867 AN: 151928 Hom.: 22094 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.493 AC: 74896 AN: 152048 Hom.: 22101 Cov.: 32 AF XY: 0.487 AC XY: 36147 AN XY: 74300

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.553

Alfa AF: 0.637 Hom.: 41630

Bravo AF: 0.489

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.53

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: rs724201; hg19: chr12-71956013;