NM_201525.4:c.-36+10408C>T

Variant names:

• chr16-57639210-C-T
• rs7187902
• NM_201525.4:c.-36+10408C>T

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+10408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 963,732 control chromosomes in the GnomAD database, including 27,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4330 hom., cov: 32)
  • Exomes 𝑓: 0.24 (22773 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49

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=-0.9).
• BP6: Variant 16-57639210-C-T is Benign according to our data. Variant chr16-57639210-C-T is described in ClinVar as [Benign]. Clinvar id is 679870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+10408C>T		intron_variant	Intron 1 of 13	ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+10408C>T		intron_variant	Intron 1 of 13	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35502 AN: 152046 Hom.: 4324 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.236 AC: 191852 AN: 811568 Hom.: 22773 AF XY: 0.236 AC XY: 88715 AN XY: 375380

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.0393

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.234 AC: 35532 AN: 152164 Hom.: 4330 Cov.: 32 AF XY: 0.232 AC XY: 17247 AN XY: 74394

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.234

Alfa AF: 0.234 Hom.: 928

Bravo AF: 0.227

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.56

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: rs7187902; hg19: chr16-57673122;