Genetic Variant NM_201525.4:c.1665-41C>T (chr16-57661656-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_201525.4(ADGRG1):c.1665-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,591,178 control chromosomes in the GnomAD database, including 27,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1954 hom., cov: 33)

Exomes 𝑓: 0.18 ( 25388 hom. )

Consequence

ADGRG1
NM_201525.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.52

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=-0.84).

BP6

Variant 16-57661656-C-T is Benign according to our data. Variant chr16-57661656-C-T is described in ClinVar as [Benign]. Clinvar id is 158623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4 link	c.1665-41C>T		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.1665-41C>T		intron_variant	Intron 12 of 13	1	NM_201525.4	ENSP00000455351.2		Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21254

AN:

152142

Hom.:

1951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.154

AC:

32003

AN:

208424

Hom.:

2805

AF XY:

0.156

AC XY:

17619

AN XY:

112926

show subpopulations

Gnomad AFR exome

AF:

0.0331

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.00161

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.182

AC:

261770

AN:

1438918

Hom.:

25388

Cov.:

AF XY:

0.182

AC XY:

129645

AN XY:

714252

show subpopulations

Gnomad4 AFR exome

AF:

0.0317

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.000963

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.140

AC:

21259

AN:

152260

Hom.:

1954

Cov.:

AF XY:

0.138

AC XY:

10282

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.120

Hom.:

346

Bravo

AF:

0.135

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 14, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bilateral frontoparietal polymicrogyria

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.028

DANN

Benign

0.71

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