11-27368475-C-T

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

Scores

6
9
3

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.87
Variant links:
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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGR4NM_018490.5 linkc.2248G>A p.Ala750Thr missense_variant Exon 18 of 18 ENST00000379214.9 NP_060960.2 Q9BXB1-1Q59ER8
LGR4NM_001346432.2 linkc.2176G>A p.Ala726Thr missense_variant Exon 17 of 17 NP_001333361.1 Q9BXB1-2Q59ER8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGR4ENST00000379214.9 linkc.2248G>A p.Ala750Thr missense_variant Exon 18 of 18 1 NM_018490.5 ENSP00000368516.4 Q9BXB1-1
LGR4ENST00000389858.4 linkc.2176G>A p.Ala726Thr missense_variant Exon 17 of 17 1 ENSP00000374508.4 Q9BXB1-2

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0162
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00156
AC:
392
AN:
251426
Hom.:
3
AF XY:
0.00131
AC XY:
178
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0204
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000977
GnomAD4 exome
AF:
0.000321
AC:
469
AN:
1461874
Hom.:
2
Cov.:
37
AF XY:
0.000307
AC XY:
223
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00909
Gnomad4 SAS exome
AF:
0.000359
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000977
GnomAD4 genome
AF:
0.000611
AC:
93
AN:
152300
Hom.:
0
Cov.:
33
AF XY:
0.000671
AC XY:
50
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0164
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000691
Hom.:
1
Bravo
AF:
0.000601
ExAC
AF:
0.00123
AC:
149
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.59
D;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D
MetaRNN
Benign
0.011
T;T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Pathogenic
3.0
M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.87
MVP
0.74
MPC
0.82
ClinPred
0.12
T
GERP RS
5.6
Varity_R
0.73
gMVP
0.78

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

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

Other links and lift over

dbSNP: rs149204548; hg19: chr11-27390022; COSMIC: COSV60821660; COSMIC: COSV60821660; API