16-57629021-C-A

Position:

• chr16-57629021-C-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+219C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 441,712 control chromosomes in the GnomAD database, including 61,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (26631 hom., cov: 28)
  • Exomes 𝑓: 0.47 (34771 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.61

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=-0.85).
• BP6: Variant 16-57629021-C-A is Benign according to our data. Variant chr16-57629021-C-A is described in ClinVar as [Benign]. Clinvar id is 1242367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+219C>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+219C>A		intron_variant		1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.589 AC: 86782 AN: 147376 Hom.: 26587 Cov.: 28

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.472 AC: 138942 AN: 294210 Hom.: 34771 AF XY: 0.473 AC XY: 65994 AN XY: 139414

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.589 AC: 86890 AN: 147502 Hom.: 26631 Cov.: 28 AF XY: 0.585 AC XY: 42039 AN XY: 71898

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.559

Alfa AF: 0.341 Hom.: 601

Bravo AF: 0.612

Asia WGS AF: 0.613 AC: 2125 AN: 3464

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

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.32

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: rs4993022; hg19: chr16-57662933; COSMIC: COSV66303273; COSMIC: COSV66303273;