Variant 11-27472121-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000379214.9(LGR4):c.182C>T(p.Ala61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,021,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

LGR4
ENST00000379214.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

LGR4-AS1 (HGNC:):

LGR4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3165371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR4	NM_018490.5 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	1/18	ENST00000379214.9	NP_060960.2	Q9BXB1-1Q59ER8
LGR4	NM_001346432.2 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	1/17		NP_001333361.1	Q9BXB1-2Q59ER8
LGR4-AS1	NR_131169.1 linkuse as main transcript	n.102+289G>A		intron_variant
LGR4-AS1	NR_131170.1 linkuse as main transcript	n.102+289G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR4	ENST00000379214.9 linkuse as main transcript	c.182C>T	p.Ala61Val	missense_variant	1/18	1	NM_018490.5	ENSP00000368516.4		Q9BXB1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000196

AC:

AN:

1021442

Hom.:

Cov.:

AF XY:

0.00000201

AC XY:

AN XY:

497336

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000232

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.182C>T (p.A61V) alteration is located in exon 1 (coding exon 1) of the LGR4 gene. This alteration results from a C to T substitution at nucleotide position 182, causing the alanine (A) at amino acid position 61 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

T;.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.69

T;T;T

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;N;.

MutationTaster

Benign

0.56

N;N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.052

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.021

B;.;.

Vest4

0.17

MutPred

0.41

Gain of catalytic residue at M66 (P = 0.0318);Gain of catalytic residue at M66 (P = 0.0318);Gain of catalytic residue at M66 (P = 0.0318);

MVP

0.29

MPC

0.23

ClinPred

0.54

GERP RS

2.3

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over