chr16-57628925-T-A

Position:

• chr16-57628925-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+123T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 144,146 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (74 hom., cov: 27)
  • Exomes 𝑓: 0.0025 (122 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.595

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]

ADGRG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-57628925-T-A is Benign according to our data. Variant chr16-57628925-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1175599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+123T>A		intron_variant		ENST00000562631.7	NP_958933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+123T>A		intron_variant		1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2453 AN: 144036 Hom.: 73 Cov.: 27

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.000444

Gnomad OTH AF: 0.0146

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00255 AC: 1556 AN: 610746 Hom.: 122 Cov.: 7 AF XY: 0.00234 AC XY: 664 AN XY: 284098

Gnomad4 AFR exome AF: 0.0555

Gnomad4 AMR exome AF: 0.00419

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.0265

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000191

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0171 AC: 2470 AN: 144146 Hom.: 74 Cov.: 27 AF XY: 0.0180 AC XY: 1263 AN XY: 70320

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.00620

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000444

Gnomad4 OTH AF: 0.0155

Alfa AF: 0.0125 Hom.: 0

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

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.42

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: rs201652072; hg19: chr16-57662837;