rs1801255

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201525.4(ADGRG1):c.918A>C(p.Gln306His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,744 control chromosomes in the GnomAD database, including 46,637 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3530 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43107 hom. )

Consequence

ADGRG1
NM_201525.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.344

Publications

21 publications found

Variant links:

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 Gene-Disease associations (from GenCC):

bilateral frontoparietal polymicrogyria
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ADGRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002811551).

BP6

Variant 16-57655893-A-C is Benign according to our data. Variant chr16-57655893-A-C is described in ClinVar as Benign. ClinVar VariationId is 158640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4 link	c.918A>C	p.Gln306His	missense_variant	Exon 7 of 14	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7 link	c.918A>C	p.Gln306His	missense_variant	Exon 7 of 14	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29790

AN:

152044

Hom.:

3530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0933

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0971

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.206

GnomAD2 exomes

AF:

0.200

AC:

50172

AN:

251470

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.0947

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.00636

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.234

AC:

341378

AN:

1461582

Hom.:

43107

Cov.:

AF XY:

0.231

AC XY:

167932

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0854

AC:

2859

AN:

33478

American (AMR)

AF:

0.127

AC:

5663

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

7448

AN:

26136

East Asian (EAS)

AF:

0.00353

AC:

140

AN:

39698

South Asian (SAS)

AF:

0.112

AC:

9665

AN:

86256

European-Finnish (FIN)

AF:

0.324

AC:

17307

AN:

53408

Middle Eastern (MID)

AF:

0.195

AC:

1122

AN:

5768

European-Non Finnish (NFE)

AF:

0.256

AC:

284159

AN:

1111722

Other (OTH)

AF:

0.216

AC:

13015

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

15000

30000

45001

60001

75001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9290

18580

27870

37160

46450

<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:

0.196

AC:

29785

AN:

152162

Hom.:

3530

Cov.:

AF XY:

0.196

AC XY:

14611

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0931

AC:

3866

AN:

41530

American (AMR)

AF:

0.161

AC:

2462

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1028

AN:

3466

East Asian (EAS)

AF:

0.00560

AC:

AN:

5178

South Asian (SAS)

AF:

0.0976

AC:

470

AN:

4816

European-Finnish (FIN)

AF:

0.347

AC:

3670

AN:

10584

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.258

AC:

17503

AN:

67970

Other (OTH)

AF:

0.204

AC:

431

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1205

2410

3615

4820

6025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.235

Hom.:

13199

Bravo

AF:

0.179

TwinsUK

AF:

0.248

AC:

920

ALSPAC

AF:

0.243

AC:

936

ESP6500AA

AF:

0.0978

AC:

430

ESP6500EA

AF:

0.266

AC:

2284

ExAC

AF:

0.200

AC:

24257

Asia WGS

AF:

0.0740

AC:

260

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bilateral frontoparietal polymicrogyria

Benign:3

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.10

.;T;T;.;.;.;.;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.63

.;.;T;.;T;.;.;T

MetaRNN

Benign

0.0028

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.34

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N;N;N;.;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.19

T;T;T;T;.;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T;T;T;T

Polyphen

0.012

B;B;B;B;.;B;B;B

Vest4

0.053

MutPred

0.13

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

ClinPred

0.0087

GERP RS

-0.62

Varity_R

0.059

gMVP

0.52

Mutation Taster

=100/0

polymorphism (auto)

(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

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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