Variant chr12-71578805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003667.4(LGR5):c.1282G>A(p.Asp428Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,603,444 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 33 hom. )

Consequence

LGR5
NM_003667.4 missense, splice_region

Scores

Splicing: ADA: 0.9781

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.15

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:

LOC124902963 (HGNC:):

LOC124902963 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-71578805-G-A is Benign according to our data. Variant chr12-71578805-G-A is described in ClinVar as [Benign]. Clinvar id is 718180.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4 linkuse as main transcript	c.1282G>A	p.Asp428Asn	missense_variant, splice_region_variant	15/18	ENST00000266674.10
LOC124902963	XR_007063365.1 linkuse as main transcript	n.126-1774C>T		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.1282G>A	p.Asp428Asn	missense_variant, splice_region_variant	15/18	1	NM_003667.4	P1	O75473-1

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

816

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000798

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00535

AC:

1305

AN:

243990

Hom.:

AF XY:

0.00535

AC XY:

705

AN XY:

131762

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00163

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000835

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.00531

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00470

AC:

6825

AN:

1451282

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3248

AN XY:

721642

show subpopulations

Gnomad4 AFR exome

AF:

0.000637

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00535

AC:

814

AN:

152162

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

482

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00307

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00507

AC:

615

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

-0.090

N;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.18

T;T;T

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.87

MVP

0.93

MPC

0.34

ClinPred

0.027

GERP RS

5.7

Varity_R

0.45

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.89

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