16-57628855-A-T

Position:

• chr16-57628855-A-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+53A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 881,016 control chromosomes in the GnomAD database, including 4,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1489 hom., cov: 33)
  • Exomes 𝑓: 0.074 (3274 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.855

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 16-57628855-A-T is Benign according to our data. Variant chr16-57628855-A-T is described in ClinVar as [Benign]. Clinvar id is 1227704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4	c.-36+53A>T		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7	c.-36+53A>T		intron_variant		1	NM_201525.4	P4
	ENST00000563251.1	n.273+1550T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20488 AN: 149982 Hom.: 1484 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.0744 AC: 54369 AN: 730918 Hom.: 3274 Cov.: 19 AF XY: 0.0743 AC XY: 25139 AN XY: 338260

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0895

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.0373

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.0823

GnomAD4 genome AF: 0.137 AC: 20515 AN: 150098 Hom.: 1489 Cov.: 33 AF XY: 0.135 AC XY: 9881 AN XY: 73358

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.140

Alfa AF: 0.128 Hom.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76652341; hg19: chr16-57662767;