Variant rs17109924 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003667.4(LGR5):c.1997T>C(p.Val666Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,614,112 control chromosomes in the GnomAD database, including 5,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.084 ( 619 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4469 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

LGR5 (HGNC:4504): (leucine rich repeat containing G protein-coupled receptor 5) The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LGR5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002444744).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.1997T>C	p.Val666Ala	missense_variant	18/18	ENST00000266674.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGR5	ENST00000266674.10 linkuse as main transcript	c.1997T>C	p.Val666Ala	missense_variant	18/18	1	NM_003667.4	P1	O75473-1
LGR5	ENST00000540815.2 linkuse as main transcript	c.1925T>C	p.Val642Ala	missense_variant	17/17	1			O75473-2
LGR5	ENST00000536515.5 linkuse as main transcript	c.1781T>C	p.Val594Ala	missense_variant	17/17	1			O75473-3
LGR5	ENST00000550851.5 linkuse as main transcript	n.2283+95T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12843

AN:

152118

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.0742

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0864

Gnomad FIN

AF:

0.0927

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0736

GnomAD3 exomes

AF:

0.0739

AC:

18592

AN:

251422

Hom.:

792

AF XY:

0.0740

AC XY:

10056

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.0706

Gnomad ASJ exome

AF:

0.0699

Gnomad EAS exome

AF:

0.00533

Gnomad SAS exome

AF:

0.0885

Gnomad FIN exome

AF:

0.0929

Gnomad NFE exome

AF:

0.0740

Gnomad OTH exome

AF:

0.0765

GnomAD4 exome

AF:

0.0756

AC:

110460

AN:

1461876

Hom.:

4469

Cov.:

AF XY:

0.0756

AC XY:

55000

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0706

Gnomad4 ASJ exome

AF:

0.0696

Gnomad4 EAS exome

AF:

0.00617

Gnomad4 SAS exome

AF:

0.0871

Gnomad4 FIN exome

AF:

0.0964

Gnomad4 NFE exome

AF:

0.0755

Gnomad4 OTH exome

AF:

0.0735

GnomAD4 genome

AF:

0.0845

AC:

12857

AN:

152236

Hom.:

619

Cov.:

AF XY:

0.0847

AC XY:

6301

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0743

Gnomad4 ASJ

AF:

0.0712

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0864

Gnomad4 FIN

AF:

0.0927

Gnomad4 NFE

AF:

0.0787

Gnomad4 OTH

AF:

0.0728

Alfa

AF:

0.0753

Hom.:

1017

Bravo

AF:

0.0821

TwinsUK

AF:

0.0677

AC:

251

ALSPAC

AF:

0.0737

AC:

284

ESP6500AA

AF:

0.103

AC:

456

ESP6500EA

AF:

0.0764

AC:

657

ExAC

AF:

0.0753

AC:

9146

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.0737

EpiControl

AF:

0.0698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.32

T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0034

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.

MutationTaster

Benign

0.86

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.035

B;.;B

Vest4

0.10

MPC

0.070

ClinPred

0.0097

GERP RS

4.7

Varity_R

0.14

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over