16-57628949-T-C

Position:

• chr16-57628949-T-C

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+147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 577,540 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (289 hom., cov: 29)
  • Exomes 𝑓: 0.0064 (208 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-57628949-T-C is Benign according to our data. Variant chr16-57628949-T-C is described in ClinVar as [Benign]. Clinvar id is 1233631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+147T>C		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+147T>C		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1456A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 6091 AN: 108584 Hom.: 286 Cov.: 29

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0469

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.00683

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0280

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0539

GnomAD4 exome AF: 0.00642 AC: 3012 AN: 468842 Hom.: 208 AF XY: 0.00650 AC XY: 1426 AN XY: 219460

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.0765

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.00617

Gnomad4 NFE exome AF: 0.00523

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0563 AC: 6119 AN: 108698 Hom.: 289 Cov.: 29 AF XY: 0.0578 AC XY: 3076 AN XY: 53236

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.00683

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0595

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.41

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: rs879574155; hg19: chr16-57662861;