chr12-71567917-T-A

Variant names:

• chr12-71567917-T-A
• rs1797376
• NM_003667.4:c.1070+1005T>A

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+1005T>A 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 152,104 control chromosomes in the GnomAD database, including 61,047 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 (61047 hom., cov: 31)
• Consequence: LGR5 NM_003667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• 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=-0.83).
• 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 rank	MANE	Protein	UniProt
LGR5	NM_003667.4	c.1070+1005T>A		intron_variant	Intron 11 of 17	ENST00000266674.10	NP_003658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10	c.1070+1005T>A		intron_variant	Intron 11 of 17	1	NM_003667.4	ENSP00000266674.4

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133952 AN: 151986 Hom.: 61014 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.988

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: 134043 AN: 152104 Hom.: 61047 Cov.: 31 AF XY: 0.884 AC XY: 65767 AN XY: 74376

African (AFR) AF: 0.625 AC: 25865 AN: 41416

American (AMR) AF: 0.949 AC: 14502 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5152 AN: 5176

South Asian (SAS) AF: 0.954 AC: 4601 AN: 4824

European-Finnish (FIN) AF: 0.976 AC: 10339 AN: 10594

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

European-Non Finnish (NFE) AF: 0.985 AC: 67031 AN: 68026

Other (OTH) AF: 0.916 AC: 1934 AN: 2112

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	-0.83
CADD	Benign	3.3
DANN	Benign	0.47
PhyloP100		-0.28
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: rs1797376; hg19: chr12-71961697;