12-71553626-A-T

Position:

• chr12-71553626-A-T

Variant summary

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

The NM_003667.4(LGR5):​c.644+338A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,130 control chromosomes in the GnomAD database, including 2,382 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 0.15 (2382 hom., cov: 32)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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]

LGR5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR5	NM_003667.4	c.644+338A>T		intron_variant		ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.644+338A>T		intron_variant		1	NM_003667.4	ENSP00000266674.4
LGR5	ENST00000540815.2	c.644+338A>T		intron_variant		1		ENSP00000441035.2
LGR5	ENST00000536515.5	c.429-2993A>T		intron_variant		1		ENSP00000443033.1
LGR5	ENST00000550851.5	n.741+338A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22831 AN: 152012 Hom.: 2365 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.150 AC: 22890 AN: 152130 Hom.: 2382 Cov.: 32 AF XY: 0.154 AC XY: 11462 AN XY: 74358

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.160

Alfa AF: 0.0255 Hom.: 18

Bravo AF: 0.159

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
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: rs11178846; hg19: chr12-71947406;