rs10852554

Positions:

• chr16-57663620-T-G

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.*38T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 1,604,006 control chromosomes in the GnomAD database, including 442,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46083 hom., cov: 35)
  • Exomes 𝑓: 0.74 (395934 hom.)
• Consequence: ADGRG1 NM_201525.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-57663620-T-G is Benign according to our data. Variant chr16-57663620-T-G is described in ClinVar as [Benign]. Clinvar id is 259865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.*38T>G		3_prime_UTR_variant	14/14	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.*38T>G		3_prime_UTR_variant	14/14	1	NM_201525.4	ENSP00000455351	P4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117310 AN: 152120 Hom.: 46031 Cov.: 35

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.760 AC: 186247 AN: 245194 Hom.: 71932 AF XY: 0.755 AC XY: 100622 AN XY: 133352

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.848

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.943

Gnomad SAS exome AF: 0.810

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.733

GnomAD4 exome AF: 0.736 AC: 1067830 AN: 1451768 Hom.: 395934 Cov.: 37 AF XY: 0.736 AC XY: 532383 AN XY: 722884

Gnomad4 AFR exome AF: 0.888

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.811

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.771 AC: 117420 AN: 152238 Hom.: 46083 Cov.: 35 AF XY: 0.767 AC XY: 57079 AN XY: 74422

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.764

Alfa AF: 0.734 Hom.: 11619

Bravo AF: 0.795

Asia WGS AF: 0.861 AC: 2994 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bilateral frontoparietal polymicrogyria Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.39

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: rs10852554; hg19: chr16-57697532; COSMIC: COSV59650806; COSMIC: COSV59650806;