chr12-71567820-A-G

Position:

• chr12-71567820-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR5	NM_003667.4	c.1070+908A>G		intron_variant		ENST00000266674.10	NP_003658.1
LOC105369833	XR_001749200.2	n.118+3813T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.1070+908A>G		intron_variant		1	NM_003667.4	ENSP00000266674	P1

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.916

Alfa AF: 0.923 Hom.: 8209

Bravo AF: 0.867

Asia WGS AF: 0.956 AC: 3325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.74

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: rs1795462; hg19: chr12-71961600;