rs74326170

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201525.4(ADGRG1):c.1286+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,604,548 control chromosomes in the GnomAD database, including 1,218 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 0.052 ( 524 hom., cov: 32)

Exomes 𝑓: 0.012 ( 694 hom. )

Consequence

ADGRG1
NM_201525.4 splice_region, intron

Scores

Splicing: ADA: 0.0003660

Clinical Significance

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

Conservation

PhyloP100: 0.224

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-57657497-G-A is Benign according to our data. Variant chr16-57657497-G-A is described in ClinVar as [Benign]. Clinvar id is 137494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57657497-G-A is described in Lovd as [Benign]. Variant chr16-57657497-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4 link	c.1286+6G>A		splice_region_variant, intron_variant	Intron 10 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.1286+6G>A		splice_region_variant, intron_variant	Intron 10 of 13	1	NM_201525.4	ENSP00000455351.2		Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7831

AN:

152138

Hom.:

520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0863

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00576

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0246

AC:

6172

AN:

251082

Hom.:

306

AF XY:

0.0219

AC XY:

2978

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0894

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.000328

Gnomad NFE exome

AF:

0.00585

Gnomad OTH exome

AF:

0.0230

GnomAD4 exome

AF:

0.0123

AC:

17871

AN:

1452292

Hom.:

694

Cov.:

AF XY:

0.0120

AC XY:

8670

AN XY:

722976

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0176

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0709

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.000642

Gnomad4 NFE exome

AF:

0.00480

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0516

AC:

7859

AN:

152256

Hom.:

524

Cov.:

AF XY:

0.0506

AC XY:

3766

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0227

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0859

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00575

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.0233

Hom.:

136

Bravo

AF:

0.0595

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00765

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 15, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 04, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bilateral frontoparietal polymicrogyria

Benign:2

Jan 12, 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. -

Sep 16, 2020

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

-0.75

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.040

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