16-57628879-T-A

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+77T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 800,780 control chromosomes in the GnomAD database, including 5,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1852 hom., cov: 32)
  • Exomes 𝑓: 0.079 (3237 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.642

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=-0.95).
• BP6: Variant 16-57628879-T-A is Benign according to our data. Variant chr16-57628879-T-A is described in ClinVar as [Benign]. Clinvar id is 1183718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+77T>A		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+77T>A		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1526A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 22445 AN: 146496 Hom.: 1846 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.0793 AC: 51890 AN: 654162 Hom.: 3237 Cov.: 4 AF XY: 0.0793 AC XY: 24024 AN XY: 302820

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0829

Gnomad4 ASJ exome AF: 0.0930

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0769

Gnomad4 OTH exome AF: 0.0872

GnomAD4 genome AF: 0.153 AC: 22480 AN: 146618 Hom.: 1852 Cov.: 32 AF XY: 0.151 AC XY: 10778 AN XY: 71554

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0873

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.154

Alfa AF: 0.139 Hom.: 43

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.2
Dann	Benign	0.16

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: rs2278807; hg19: chr16-57662791;