11-27368475-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3BP4_StrongBP6_ModerateBS2_Supporting
The NM_018490.5(LGR4):c.2248G>A(p.Ala750Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,614,174 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 2 hom. )
Consequence
LGR4
NM_018490.5 missense
NM_018490.5 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 7.87
Genes affected
LGR4 (HGNC:13299): (leucine rich repeat containing G protein-coupled receptor 4) The protein encoded by this gene is a G-protein coupled receptor that binds R-spondins and activates the Wnt signaling pathway. This Wnt signaling pathway activation is necessary for proper development of many organs of the body. [provided by RefSeq, Oct 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Dann, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.011096895).
BP6
Variant 11-27368475-C-T is Benign according to our data. Variant chr11-27368475-C-T is described in ClinVar as [Benign]. Clinvar id is 713249.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 93 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LGR4 | ENST00000379214.9 | c.2248G>A | p.Ala750Thr | missense_variant | Exon 18 of 18 | 1 | NM_018490.5 | ENSP00000368516.4 | ||
LGR4 | ENST00000389858.4 | c.2176G>A | p.Ala726Thr | missense_variant | Exon 17 of 17 | 1 | ENSP00000374508.4 |
Frequencies
GnomAD3 genomes AF: 0.000605 AC: 92AN: 152182Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
92
AN:
152182
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00156 AC: 392AN: 251426Hom.: 3 AF XY: 0.00131 AC XY: 178AN XY: 135882
GnomAD3 exomes
AF:
AC:
392
AN:
251426
Hom.:
AF XY:
AC XY:
178
AN XY:
135882
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000321 AC: 469AN: 1461874Hom.: 2 Cov.: 37 AF XY: 0.000307 AC XY: 223AN XY: 727236
GnomAD4 exome
AF:
AC:
469
AN:
1461874
Hom.:
Cov.:
37
AF XY:
AC XY:
223
AN XY:
727236
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000611 AC: 93AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.000671 AC XY: 50AN XY: 74476
GnomAD4 genome
AF:
AC:
93
AN:
152300
Hom.:
Cov.:
33
AF XY:
AC XY:
50
AN XY:
74476
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
149
Asia WGS
AF:
AC:
22
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at