Variant rs1376041 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_201525.4(ADGRG1):c.996T>C(p.Thr332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,613,752 control chromosomes in the GnomAD database, including 423,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 48353 hom., cov: 33)

Exomes 𝑓: 0.71 ( 375041 hom. )

Consequence

ADGRG1
NM_201525.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.183

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 16-57655971-T-C is Benign according to our data. Variant chr16-57655971-T-C is described in ClinVar as [Benign]. Clinvar id is 158641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57655971-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4 linkuse as main transcript	c.996T>C	p.Thr332=	synonymous_variant	7/14	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7 linkuse as main transcript	c.996T>C	p.Thr332=	synonymous_variant	7/14	1	NM_201525.4	ENSP00000455351	P4	Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120161

AN:

152112

Hom.:

48301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.735

Gnomad EAS

AF:

0.797

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.782

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.773

GnomAD3 exomes

AF:

0.759

AC:

190874

AN:

251354

Hom.:

73508

AF XY:

0.745

AC XY:

101190

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.951

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.746

Gnomad EAS exome

AF:

0.809

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.765

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.741

GnomAD4 exome

AF:

0.714

AC:

1043920

AN:

1461522

Hom.:

375041

Cov.:

AF XY:

0.712

AC XY:

517343

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.955

Gnomad4 AMR exome

AF:

0.889

Gnomad4 ASJ exome

AF:

0.740

Gnomad4 EAS exome

AF:

0.776

Gnomad4 SAS exome

AF:

0.675

Gnomad4 FIN exome

AF:

0.760

Gnomad4 NFE exome

AF:

0.697

Gnomad4 OTH exome

AF:

0.728

GnomAD4 genome

AF:

0.790

AC:

120272

AN:

152230

Hom.:

48353

Cov.:

AF XY:

0.794

AC XY:

59129

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.944

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.735

Gnomad4 EAS

AF:

0.796

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.782

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.771

Alfa

AF:

0.726

Hom.:

66302

Bravo

AF:

0.806

Asia WGS

AF:

0.762

AC:

2648

AN:

3478

EpiCase

AF:

0.700

EpiControl

AF:

0.710

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bilateral frontoparietal polymicrogyria

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.5

DANN

Benign

0.47

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