16-57628919-TGA-T

Variant names:

• chr16-57628919-TGA-T
• rs879762315
• NM_201525.4:c.-36+119_-36+120delAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_201525.4(ADGRG1):​c.-36+119_-36+120delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 87,366 control chromosomes in the GnomAD database, including 288 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (288 hom., cov: 25)
  • Exomes 𝑓: 0.0051 (271 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000261633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-57628919-TGA-T is Benign according to our data. Variant chr16-57628919-TGA-T is described in ClinVar as Benign. ClinVar VariationId is 1296044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	NM_201525.4	MANE Select	c.-36+119_-36+120delAG		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+119_-154+120delAG		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9040_-154+9041delAG		intron	N/A	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.-36+118_-36+119delGA		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8784_-154+8785delGA		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+92_-154+93delGA		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 6136 AN: 87314 Hom.: 285 Cov.: 25

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0487

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.00763

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0326

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0627

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00508 AC: 3139 AN: 618402 Hom.: 271 AF XY: 0.00503 AC XY: 1447 AN XY: 287882

African (AFR) AF: 0.0313 AC: 318 AN: 10152

American (AMR) AF: 0.0228 AC: 16 AN: 702

Ashkenazi Jewish (ASJ) AF: 0.000782 AC: 3 AN: 3838

East Asian (EAS) AF: 0.0762 AC: 180 AN: 2362

South Asian (SAS) AF: 0.0103 AC: 123 AN: 11960

European-Finnish (FIN) AF: 0.00463 AC: 1 AN: 216

Middle Eastern (MID) AF: 0.00254 AC: 3 AN: 1180

European-Non Finnish (NFE) AF: 0.00408 AC: 2318 AN: 568118

Other (OTH) AF: 0.00891 AC: 177 AN: 19874

GnomAD4 genome AF: 0.0706 AC: 6164 AN: 87366 Hom.: 288 Cov.: 25 AF XY: 0.0723 AC XY: 3102 AN XY: 42896

African (AFR) AF: 0.181 AC: 2794 AN: 15420

American (AMR) AF: 0.103 AC: 1033 AN: 10034

Ashkenazi Jewish (ASJ) AF: 0.00763 AC: 16 AN: 2096

East Asian (EAS) AF: 0.258 AC: 936 AN: 3632

South Asian (SAS) AF: 0.0521 AC: 151 AN: 2898

European-Finnish (FIN) AF: 0.0313 AC: 226 AN: 7228

Middle Eastern (MID) AF: 0.0291 AC: 5 AN: 172

European-Non Finnish (NFE) AF: 0.0201 AC: 885 AN: 44022

Other (OTH) AF: 0.0695 AC: 91 AN: 1310

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs879762315; hg19: chr16-57662831;