12-71567820-A-G

Variant names:

• chr12-71567820-A-G
• rs1795462
• NM_003667.4:c.1070+908A>G

Variant summary

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

The NM_003667.4(LGR5):​c.1070+908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,094 control chromosomes in the GnomAD database, including 61,042 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 0.88 (61042 hom., cov: 31)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	NM_003667.4	MANE Select	c.1070+908A>G		intron	N/A	NP_003658.1	O75473-1
	LGR5	NM_001277226.2		c.998+908A>G		intron	N/A	NP_001264155.1	O75473-2
	LGR5	NM_001277227.2		c.854+908A>G		intron	N/A	NP_001264156.1	O75473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGR5	ENST00000266674.10	TSL:1 MANE Select	c.1070+908A>G		intron	N/A	ENSP00000266674.4	O75473-1
	LGR5	ENST00000540815.2	TSL:1	c.998+908A>G		intron	N/A	ENSP00000441035.2	O75473-2
	LGR5	ENST00000536515.5	TSL:1	c.854+908A>G		intron	N/A	ENSP00000443033.1	O75473-3

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133940 AN: 151976 Hom.: 61009 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.881 AC: 134031 AN: 152094 Hom.: 61042 Cov.: 31 AF XY: 0.884 AC XY: 65744 AN XY: 74358

African (AFR) AF: 0.624 AC: 25860 AN: 41416

American (AMR) AF: 0.949 AC: 14497 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3431 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5164 AN: 5188

South Asian (SAS) AF: 0.954 AC: 4605 AN: 4828

European-Finnish (FIN) AF: 0.976 AC: 10336 AN: 10592

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67021 AN: 68016

Other (OTH) AF: 0.916 AC: 1930 AN: 2108

Alfa AF: 0.911 Hom.: 8367

Bravo AF: 0.867

Asia WGS AF: 0.956 AC: 3325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		0.60
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: rs1795462; hg19: chr12-71961600;