chr12-71566909-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003667.4(LGR5):ā€‹c.1067T>Gā€‹(p.Val356Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LGR5NM_003667.4 linkuse as main transcriptc.1067T>G p.Val356Gly missense_variant 11/18 ENST00000266674.10 NP_003658.1
LOC105369833XR_001749200.2 linkuse as main transcriptn.118+4724A>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LGR5ENST00000266674.10 linkuse as main transcriptc.1067T>G p.Val356Gly missense_variant 11/181 NM_003667.4 ENSP00000266674 P1O75473-1
LGR5ENST00000540815.2 linkuse as main transcriptc.995T>G p.Val332Gly missense_variant 10/171 ENSP00000441035 O75473-2
LGR5ENST00000536515.5 linkuse as main transcriptc.851T>G p.Val284Gly missense_variant 10/171 ENSP00000443033 O75473-3
LGR5ENST00000550851.5 linkuse as main transcriptn.1164T>G non_coding_transcript_exon_variant 11/202

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251222
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135780
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1457760
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725492
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 05, 2024The c.1067T>G (p.V356G) alteration is located in exon 11 (coding exon 11) of the LGR5 gene. This alteration results from a T to G substitution at nucleotide position 1067, causing the valine (V) at amino acid position 356 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.88
D;T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.5
L;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.6
D;D;D
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.62
P;.;B
Vest4
0.42
MutPred
0.56
Gain of catalytic residue at P352 (P = 0.0159);.;.;
MVP
0.65
MPC
0.34
ClinPred
0.94
D
GERP RS
5.7
Varity_R
0.84
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.25
Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766384127; hg19: chr12-71960689; API