16-57628953-A-T

Position:

• chr16-57628953-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_201525.4(ADGRG1):​c.-36+151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 585,454 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 26)
  • Exomes 𝑓: 0.015 (17 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636

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=-0.88).
• BP6: Variant 16-57628953-A-T is Benign according to our data. Variant chr16-57628953-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1254765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00365 (375/102616) while in subpopulation AFR AF= 0.00827 (203/24536). AF 95% confidence interval is 0.00734. There are 2 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+151A>T		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+151A>T		intron_variant		1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 371 AN: 102548 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00814

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00153

Gnomad ASJ AF: 0.00672

Gnomad EAS AF: 0.000992

Gnomad SAS AF: 0.00448

Gnomad FIN AF: 0.000667

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.00227

Gnomad OTH AF: 0.00349

GnomAD4 exome AF: 0.0146 AC: 7051 AN: 482838 Hom.: 17 AF XY: 0.0148 AC XY: 3349 AN XY: 225906

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.00868

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.00340

Gnomad4 SAS exome AF: 0.00902

Gnomad4 FIN exome AF: 0.00588

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.00365 AC: 375 AN: 102616 Hom.: 2 Cov.: 26 AF XY: 0.00390 AC XY: 195 AN XY: 49984

Gnomad4 AFR AF: 0.00827

Gnomad4 AMR AF: 0.00153

Gnomad4 ASJ AF: 0.00672

Gnomad4 EAS AF: 0.000994

Gnomad4 SAS AF: 0.00448

Gnomad4 FIN AF: 0.000667

Gnomad4 NFE AF: 0.00227

Gnomad4 OTH AF: 0.00347

Alfa AF: 0.180 Hom.: 1

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

Feb 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.53

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: rs796883107; hg19: chr16-57662865;