Variant chr12-71556627-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003667.4(LGR5):c.653A>G(p.His218Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,608,868 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H218Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 10 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.22

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:

LOC105369833 (HGNC:):

LOC105369833 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014073074).

BP6

Variant 12-71556627-A-G is Benign according to our data. Variant chr12-71556627-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 715913.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.653A>G	p.His218Arg	missense_variant	6/18	ENST00000266674.10
LOC105369833	XR_001749200.2 linkuse as main transcript	n.118+15006T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGR5	ENST00000266674.10 linkuse as main transcript	c.653A>G	p.His218Arg	missense_variant	6/18	1	NM_003667.4	P1	O75473-1
LGR5	ENST00000540815.2 linkuse as main transcript	c.653A>G	p.His218Arg	missense_variant	6/17	1			O75473-2
LGR5	ENST00000536515.5 linkuse as main transcript	c.437A>G	p.His146Arg	missense_variant	5/17	1			O75473-3
LGR5	ENST00000550851.5 linkuse as main transcript	n.750A>G		non_coding_transcript_exon_variant	6/20	2

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00235

AC:

590

AN:

251284

Hom.:

AF XY:

0.00240

AC XY:

326

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00363

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00240

AC:

3490

AN:

1456556

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

1789

AN XY:

724954

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00244

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152312

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00329

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00175

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00272

AC:

330

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.092

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

N;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-6.5

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.046

D;D;D

Sift4G

Uncertain

0.058

T;D;T

Polyphen

0.12

B;.;B

Vest4

0.52

MVP

0.78

MPC

0.063

ClinPred

0.075

GERP RS

4.4

Varity_R

0.72

gMVP

0.59

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