16-57628943-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+145_-36+146del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 663,908 control chromosomes in the GnomAD database, including 505 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (290 hom., cov: 29)
  • Exomes 𝑓: 0.0052 (215 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.647

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 16-57628943-TGA-T is Benign according to our data. Variant chr16-57628943-TGA-T is described in ClinVar as [Benign]. Clinvar id is 1246748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+145_-36+146del		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+145_-36+146del		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1460_273+1461del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 6104 AN: 130974 Hom.: 287 Cov.: 29

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.0338

Gnomad AMR AF: 0.0743

Gnomad ASJ AF: 0.00506

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0342

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.00520 AC: 2772 AN: 532812 Hom.: 215 AF XY: 0.00521 AC XY: 1297 AN XY: 249014

Gnomad4 AFR exome AF: 0.0344

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.000897

Gnomad4 EAS exome AF: 0.0736

Gnomad4 SAS exome AF: 0.00962

Gnomad4 FIN exome AF: 0.00515

Gnomad4 NFE exome AF: 0.00415

Gnomad4 OTH exome AF: 0.00946

GnomAD4 genome AF: 0.0468 AC: 6132 AN: 131096 Hom.: 290 Cov.: 29 AF XY: 0.0483 AC XY: 3088 AN XY: 63912

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.00506

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0493

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: rs879732099; hg19: chr16-57662855;