16-57628937-TGAGC-T

Position:

• chr16-57628937-TGAGC-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+137_-36+140del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 774,652 control chromosomes in the GnomAD database, including 490 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (290 hom., cov: 26)
  • Exomes 𝑓: 0.0045 (200 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.587

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 16-57628937-TGAGC-T is Benign according to our data. Variant chr16-57628937-TGAGC-T is described in ClinVar as [Benign]. Clinvar id is 1233511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+137_-36+140del		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+137_-36+140del		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1464_273+1467del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6100 AN: 137366 Hom.: 287 Cov.: 26

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.0338

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.00494

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0423

GnomAD4 exome AF: 0.00454 AC: 2892 AN: 637160 Hom.: 200 AF XY: 0.00455 AC XY: 1349 AN XY: 296652

Gnomad4 AFR exome AF: 0.0282

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.000763

Gnomad4 EAS exome AF: 0.0670

Gnomad4 SAS exome AF: 0.00847

Gnomad4 FIN exome AF: 0.00435

Gnomad4 NFE exome AF: 0.00364

Gnomad4 OTH exome AF: 0.00821

GnomAD4 genome AF: 0.0446 AC: 6128 AN: 137492 Hom.: 290 Cov.: 26 AF XY: 0.0458 AC XY: 3084 AN XY: 67316

Gnomad4 AFR AF: 0.0792

Gnomad4 AMR AF: 0.0721

Gnomad4 ASJ AF: 0.00494

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0000843 Hom.: 0

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: rs879311358; hg19: chr16-57662849;