rs2290177

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.1665-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,611,276 control chromosomes in the GnomAD database, including 40,395 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3874 hom., cov: 33)

Exomes 𝑓: 0.22 ( 36521 hom. )

Consequence

ADGRG1
NM_201525.4 splice_region, intron

Scores

Splicing: ADA: 0.00001573

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.43

Publications

9 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:

ENSG00000306939 (HGNC:):

ENSG00000306939 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 (BayesDel_noAF=-0.69).

BP6

Variant 16-57661692-C-T is Benign according to our data. Variant chr16-57661692-C-T is described in ClinVar as Benign. ClinVar VariationId is 158624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4 link	c.1665-5C>T		splice_region_variant, intron_variant	Intron 12 of 13	ENST00000562631.7	NP_958933.1	Q9Y653-2A0A0S2Z517

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7 link	c.1665-5C>T		splice_region_variant, intron_variant	Intron 12 of 13	1	NM_201525.4	ENSP00000455351.2		Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32591

AN:

152074

Hom.:

3868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.256

AC:

61999

AN:

242228

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.420

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.215

AC:

313739

AN:

1459084

Hom.:

36521

Cov.:

AF XY:

0.215

AC XY:

155818

AN XY:

725834

show subpopulations

African (AFR)

AF:

0.167

AC:

5584

AN:

33414

American (AMR)

AF:

0.402

AC:

17765

AN:

44212

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

5372

AN:

26078

East Asian (EAS)

AF:

0.474

AC:

18771

AN:

39626

South Asian (SAS)

AF:

0.218

AC:

18729

AN:

86088

European-Finnish (FIN)

AF:

0.209

AC:

11061

AN:

53042

Middle Eastern (MID)

AF:

0.224

AC:

1281

AN:

5714

European-Non Finnish (NFE)

AF:

0.200

AC:

221955

AN:

1110636

Other (OTH)

AF:

0.219

AC:

13221

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

13481

26962

40444

53925

67406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7928

15856

23784

31712

39640

<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:

0.214

AC:

32618

AN:

152192

Hom.:

3874

Cov.:

AF XY:

0.220

AC XY:

16365

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.162

AC:

6735

AN:

41526

American (AMR)

AF:

0.321

AC:

4914

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

703

AN:

3470

East Asian (EAS)

AF:

0.486

AC:

2518

AN:

5180

South Asian (SAS)

AF:

0.222

AC:

1070

AN:

4820

European-Finnish (FIN)

AF:

0.211

AC:

2236

AN:

10580

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13662

AN:

68012

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1287

2574

3862

5149

6436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.212

Hom.:

5393

Bravo

AF:

0.225

Asia WGS

AF:

0.323

AC:

1122

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

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

- -

Bilateral frontoparietal polymicrogyria

Benign:3

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.65

(source)

DANN

Benign

0.75

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.012

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