16-57628720-C-G

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.-118C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 985,510 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (136 hom., cov: 33)
  • Exomes 𝑓: 0.014 (179 hom.)
• Consequence: ADGRG1 NM_201525.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

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=-0.75).
• BP6: Variant 16-57628720-C-G is Benign according to our data. Variant chr16-57628720-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1254855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-118C>G		5_prime_UTR_variant	1/14	ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-118C>G		5_prime_UTR_variant	1/14	1	NM_201525.4	P4
	ENST00000563251.1	n.274-1431G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4015 AN: 152208 Hom.: 133 Cov.: 33

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0144 AC: 11978 AN: 833184 Hom.: 179 Cov.: 31 AF XY: 0.0142 AC XY: 5474 AN XY: 384768

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.00194

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0179

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0231

GnomAD4 genome AF: 0.0265 AC: 4033 AN: 152326 Hom.: 136 Cov.: 33 AF XY: 0.0280 AC XY: 2083 AN XY: 74490

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.0296

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0177 Hom.: 8

Bravo AF: 0.0321

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.75
Cadd	Benign	7.1
Dann	Benign	0.89

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: rs28364782; hg19: chr16-57662632;