chr16-57661692-C-T

Position:

chr16-57661692-C-T

Variant summary

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

The NM_201525.4(ADGRG1):c.1665-5C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001573

Clinical Significance

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

Conservation

PhyloP100: -1.43

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=-0.69).

BP6

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

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/exons	MANE	UniProt
ADGRG1	NM_201525.4 linkuse as main transcript	c.1665-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7 linkuse as main transcript	c.1665-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_201525.4	P4	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

GnomAD3 exomes

AF:

0.256

AC:

61999

AN:

242228

Hom.:

9181

AF XY:

0.248

AC XY:

32519

AN XY:

131224

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 SAS exome

AF:

0.221

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

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.474

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.214

AC:

32618

AN:

152192

Hom.:

3874

Cov.:

AF XY:

0.220

AC XY:

16365

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.162

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.210

Hom.:

4318

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
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:3

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

Bilateral frontoparietal polymicrogyria

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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

-0.69

CADD

Benign

0.65

DANN

Benign

0.75

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

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