dbSNP rs12303775: LGR5:p.His383Arg (chr12-71572861-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003667.4(LGR5):c.1148A>G(p.His383Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000451 in 1,613,476 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

LGR5
NM_003667.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.38

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012339592).

BP6

Variant 12-71572861-A-G is Benign according to our data. Variant chr12-71572861-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 790667.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGR5	NM_003667.4 link	c.1148A>G	p.His383Arg	missense_variant	Exon 13 of 18	ENST00000266674.10	NP_003658.1	O75473-1A0A0A8K8C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGR5	ENST00000266674.10 link	c.1148A>G	p.His383Arg	missense_variant	Exon 13 of 18	1	NM_003667.4	ENSP00000266674.4		O75473-1

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

366

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00849

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000613

AC:

154

AN:

251204

AF XY:

0.000479

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000248

AC:

362

AN:

1461150

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.00920

AC:

308

AN:

33468

American (AMR)

AF:

0.000291

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111406

Other (OTH)

AF:

0.000513

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00240

AC:

366

AN:

152326

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00847

AC:

352

AN:

41574

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000955

Hom.:

Bravo

AF:

0.00300

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.39

T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.38

N;.;.

PhyloP100

5.4

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Benign

0.15

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.078

B;.;B

Vest4

0.41

MVP

0.63

MPC

0.090

ClinPred

0.058

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.66

gMVP

0.54

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over