Variant 11-27472254-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018490.5(LGR4):c.49G>T(p.Gly17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LGR4
NM_018490.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0320

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:40629): (LGR4 antisense RNA 1)

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=0.2764619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LGR4	NM_018490.5 linkuse as main transcript	c.49G>T	p.Gly17Cys	missense_variant	1/18	ENST00000379214.9	NP_060960.2
LGR4-AS1	NR_131170.1 linkuse as main transcript	n.102+422C>A		intron_variant, non_coding_transcript_variant
LGR4	NM_001346432.2 linkuse as main transcript	c.49G>T	p.Gly17Cys	missense_variant	1/17		NP_001333361.1
LGR4-AS1	NR_131169.1 linkuse as main transcript	n.102+422C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR4	ENST00000379214.9 linkuse as main transcript	c.49G>T	p.Gly17Cys	missense_variant	1/18	1	NM_018490.5	ENSP00000368516	P1	Q9BXB1-1
LGR4-AS1	ENST00000529258.1 linkuse as main transcript	n.35+422C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1159528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

564900

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:

0.00

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

Apr 07, 2023

The c.49G>T (p.G17C) alteration is located in exon 1 (coding exon 1) of the LGR4 gene. This alteration results from a G to T substitution at nucleotide position 49, causing the glycine (G) at amino acid position 17 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.074

T;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.63

T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.97

L;L;.

MutationTaster

Benign

0.81

N;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.25

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.081

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.98

D;.;.

Vest4

0.15

MutPred

0.27

Loss of glycosylation at S18 (P = 0.0616);Loss of glycosylation at S18 (P = 0.0616);Loss of glycosylation at S18 (P = 0.0616);

MVP

0.51

MPC

0.24

ClinPred

0.39

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.45

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

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