12-71553626-A-T

Variant names:

• chr12-71553626-A-T
• rs11178846
• NM_003667.4:c.644+338A>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003667.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	NM_003667.4	MANE Select	c.644+338A>T		intron	N/A	NP_003658.1
	LGR5	NM_001277226.2		c.644+338A>T		intron	N/A	NP_001264155.1
	LGR5	NM_001277227.2		c.429-2993A>T		intron	N/A	NP_001264156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.644+338A>T		intron	N/A	ENSP00000266674.4
	LGR5	ENST00000540815.2	TSL:1	c.644+338A>T		intron	N/A	ENSP00000441035.2
	LGR5	ENST00000536515.5	TSL:1	c.429-2993A>T		intron	N/A	ENSP00000443033.1

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

African (AFR) AF: 0.248 AC: 10303 AN: 41500

American (AMR) AF: 0.151 AC: 2302 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3466

East Asian (EAS) AF: 0.385 AC: 1983 AN: 5148

South Asian (SAS) AF: 0.266 AC: 1280 AN: 4814

European-Finnish (FIN) AF: 0.0781 AC: 828 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5280 AN: 67998

Other (OTH) AF: 0.160 AC: 337 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.76
PhyloP100		1.5
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: rs11178846; hg19: chr12-71947406;