Variant 11-27368673-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018490.5(LGR4):c.2050A>G(p.Arg684Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,613,876 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 74 hom. )

Consequence

LGR4
NM_018490.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.163

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]

LGR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012637377).

BP6

Variant 11-27368673-T-C is Benign according to our data. Variant chr11-27368673-T-C is described in ClinVar as [Benign]. Clinvar id is 719745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR4	NM_018490.5 link	c.2050A>G	p.Arg684Gly	missense_variant	18/18	ENST00000379214.9	NP_060960.2	Q9BXB1-1Q59ER8
LGR4	NM_001346432.2 link	c.1978A>G	p.Arg660Gly	missense_variant	17/17		NP_001333361.1	Q9BXB1-2Q59ER8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR4	ENST00000379214.9 link	c.2050A>G	p.Arg684Gly	missense_variant	18/18	1	NM_018490.5	ENSP00000368516.4		Q9BXB1-1
LGR4	ENST00000389858.4 link	c.1978A>G	p.Arg660Gly	missense_variant	17/17	1		ENSP00000374508.4		Q9BXB1-2

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2370

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00420

AC:

1054

AN:

250956

Hom.:

AF XY:

0.00324

AC XY:

440

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00157

AC:

2302

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

970

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0557

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.0156

AC:

2368

AN:

152268

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1123

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0543

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.0178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0547

AC:

241

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00484

AC:

588

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.7

DANN

Benign

0.88

DEOGEN2

Benign

0.079

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.038

Sift

Benign

0.64

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0

B;.

Vest4

0.033

MVP

0.10

MPC

0.28

ClinPred

0.0011

GERP RS

-4.1

Varity_R

0.047

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over