Variant rs61737422 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003667.4(LGR5):c.2653G>A(p.Val885Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,088 control chromosomes in the GnomAD database, including 46 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.

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0370

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:

LGR5 (HGNC:):

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=0.0023320317).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1539/152230) while in subpopulation AFR AF= 0.0345 (1432/41514). AF 95% confidence interval is 0.033. There are 19 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.2653G>A	p.Val885Met	missense_variant	18/18	ENST00000266674.10	NP_003658.1	O75473-1A0A0A8K8C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LGR5	ENST00000266674.10 linkuse as main transcript	c.2653G>A	p.Val885Met	missense_variant	18/18	1	NM_003667.4	ENSP00000266674.4	O75473-1
LGR5	ENST00000540815.2 linkuse as main transcript	c.2581G>A	p.Val861Met	missense_variant	17/17	1		ENSP00000441035.2	O75473-2
LGR5	ENST00000536515.5 linkuse as main transcript	c.2437G>A	p.Val813Met	missense_variant	17/17	1		ENSP00000443033.1	O75473-3
LGR5	ENST00000550851.5 linkuse as main transcript	n.2452G>A		non_coding_transcript_exon_variant	20/20	2

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1536

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00246

AC:

619

AN:

251440

Hom.:

AF XY:

0.00169

AC XY:

230

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00106

AC:

1556

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000903

AC XY:

657

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0332

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.00233

GnomAD4 genome

AF:

0.0101

AC:

1539

AN:

152230

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

720

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.0116

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00308

AC:

374

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.43

DANN

Benign

0.32

DEOGEN2

Benign

0.081

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.51

N;N;N

REVEL

Benign

0.030

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0070

B;.;B

Vest4

0.053

MVP

0.38

MPC

0.052

ClinPred

0.0038

GERP RS

-5.2

Varity_R

0.027

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over