Variant 1-202304570-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001017403.2(LGR6):c.1010G>A(p.Arg337His) variant causes a missense change. The variant allele was found at a frequency of 0.000672 in 1,609,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

LGR6
NM_001017403.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.04

Variant links:

Genes affected

LGR6 (HGNC:19719): (leucine rich repeat containing G protein-coupled receptor 6) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

LGR6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008629769).

BP6

Variant 1-202304570-G-A is Benign according to our data. Variant chr1-202304570-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 788947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGR6	NM_001017403.2 linkuse as main transcript	c.1010G>A	p.Arg337His	missense_variant	11/18	ENST00000367278.8	NP_001017403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGR6	ENST00000367278.8 linkuse as main transcript	c.1010G>A	p.Arg337His	missense_variant	11/18	1	NM_001017403.2	ENSP00000356247	P1	Q9HBX8-3

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00879

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00103

AC:

259

AN:

250614

Hom.:

AF XY:

0.000893

AC XY:

121

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000958

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00180

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000464

AC:

676

AN:

1456766

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

300

AN XY:

724790

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000681

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152284

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00886

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000818

Hom.:

Bravo

AF:

0.00320

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00115

AC:

140

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	LGR6: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.;.

Eigen

Benign

0.068

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D;D

MetaRNN

Benign

0.0086

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

L;.;.;.

MutationTaster

Benign

0.71

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.086

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.43

B;B;.;B

Vest4

0.37

MVP

0.83

MPC

0.62

ClinPred

0.040

GERP RS

5.5

Varity_R

0.16

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