16-57628977-AGAGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_201525.4(ADGRG1):c.-36+183_-36+186del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 466,782 control chromosomes in the GnomAD database, including 16,826 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (4458 hom., cov: 0)
  • Exomes 𝑓: 0.24 (12368 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-57628977-AGAGT-A is Benign according to our data. Variant chr16-57628977-AGAGT-A is described in ClinVar as [Benign]. Clinvar id is 1235508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+183_-36+186del		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+183_-36+186del		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1424_273+1427del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 36582 AN: 122876 Hom.: 4461 Cov.: 0

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.243 AC: 83450 AN: 343828 Hom.: 12368 AF XY: 0.243 AC XY: 39401 AN XY: 161866

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.298 AC: 36609 AN: 122954 Hom.: 4458 Cov.: 0 AF XY: 0.297 AC XY: 17790 AN XY: 59956

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.298

Alfa AF: 0.247 Hom.: 366

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs140750525; hg19: chr16-57662889;