Variant 12-71572861-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.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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id is 790667.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.1148A>G	p.His383Arg	missense_variant	13/18	ENST00000266674.10
LOC105369833	XR_001749200.2 linkuse as main transcript	n.22-1132T>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.1148A>G	p.His383Arg	missense_variant	13/18	1	NM_003667.4	P1	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

GnomAD3 exomes

AF:

0.000613

AC:

154

AN:

251204

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

135770

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.00920

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00240

AC:

366

AN:

152326

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00847

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000438

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

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

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;.;.

MutationTaster

Benign

0.99

D;D;D

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

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