chr16-57628919-TGA-T

Position:

• chr16-57628919-TGA-T

Variant summary

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

The NM_201525.4(ADGRG1):​c.-36+119_-36+120del 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

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 16-57628919-TGA-T is Benign according to our data. Variant chr16-57628919-TGA-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+119_-36+120del		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+119_-36+120del		intron_variant		1	NM_201525.4	ENSP00000455351	P4
	ENST00000563251.1	n.273+1484_273+1485del		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.000782

Gnomad4 EAS exome AF: 0.0762

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.00463

Gnomad4 NFE exome AF: 0.00408

Gnomad4 OTH exome AF: 0.00891

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

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.00763

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.0521

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0695

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

Feb 24, 2021

- -

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: rs879762315; hg19: chr16-57662831;