16-57628915-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201525.4(ADGRG1):c.-36+113A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 794,682 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (283 hom., cov: 30)
  • Exomes 𝑓: 0.0060 (348 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-57628915-A-T is Benign according to our data. Variant chr16-57628915-A-T is described in ClinVar as [Benign]. Clinvar id is 1295202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+113A>T		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+113A>T		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1490T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 6115 AN: 90070 Hom.: 280 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0486

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.00754

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0309

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0596

GnomAD4 exome AF: 0.00599 AC: 4222 AN: 704546 Hom.: 348 Cov.: 11 AF XY: 0.00608 AC XY: 1987 AN XY: 326874

Gnomad4 AFR exome AF: 0.0336

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.00227

Gnomad4 EAS exome AF: 0.0735

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00379

Gnomad4 NFE exome AF: 0.00501

Gnomad4 OTH exome AF: 0.00992

GnomAD4 genome AF: 0.0682 AC: 6143 AN: 90136 Hom.: 283 Cov.: 30 AF XY: 0.0697 AC XY: 3094 AN XY: 44372

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.00754

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0660

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.4
Dann	Benign	0.21

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: rs796979216; hg19: chr16-57662827;