16-57628904-G-A

Position:

• chr16-57628904-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201525.4(ADGRG1):​c.-36+102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 845,394 control chromosomes in the GnomAD database, including 950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (390 hom., cov: 32)
  • Exomes 𝑓: 0.012 (560 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.747

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-57628904-G-A is Benign according to our data. Variant chr16-57628904-G-A is described in ClinVar as [Benign]. Clinvar id is 1295857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+102G>A		intron_variant		ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+102G>A		intron_variant		1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 7196 AN: 108794 Hom.: 387 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0405

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.00660

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0585

GnomAD4 exome AF: 0.0119 AC: 8772 AN: 736522 Hom.: 560 Cov.: 12 AF XY: 0.0119 AC XY: 4056 AN XY: 341700

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.0272

Gnomad4 ASJ exome AF: 0.00766

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.00730

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0664 AC: 7226 AN: 108872 Hom.: 390 Cov.: 32 AF XY: 0.0677 AC XY: 3602 AN XY: 53212

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.00660

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.00452 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.33

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: rs796335861; hg19: chr16-57662816;