rs111939130

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_201525.4(ADGRG1):c.1983T>C(p.Gly661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,572 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

ADGRG1
NM_201525.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -0.987

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-57663501-T-C is Benign according to our data. Variant chr16-57663501-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 194522.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2, Likely_benign=1}. Variant chr16-57663501-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.987 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4 linkuse as main transcript	c.1983T>C	p.Gly661=	synonymous_variant	14/14	ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7 linkuse as main transcript	c.1983T>C	p.Gly661=	synonymous_variant	14/14	1	NM_201525.4	P4	Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000292

AC:

AN:

249632

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.00367

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461308

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.00317

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152264

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.00117

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 11, 2018	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 11, 2015

- -

Bilateral frontoparietal polymicrogyria

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Jan 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

1.3

Dann

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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