chr16-57628953-A-G

Variant names:

• chr16-57628953-A-G
• rs796883107
• NM_201525.4:c.-36+151A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201525.4(ADGRG1):​c.-36+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• bilateral frontoparietal polymicrogyria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ENSG00000261633 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4	c.-36+151A>G		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+151A>G		intron_variant	Intron 1 of 13	1	NM_201525.4	ENSP00000455351.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 484634 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 226764

African (AFR) AF: 0.00 AC: 0 AN: 7648

American (AMR) AF: 0.00 AC: 0 AN: 578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3066

East Asian (EAS) AF: 0.00 AC: 0 AN: 2062

South Asian (SAS) AF: 0.00 AC: 0 AN: 10014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 980

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 444420

Other (OTH) AF: 0.00 AC: 0 AN: 15696

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.46
PhyloP100		-0.64
PromoterAI		-0.0059	Neutral

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

Other links and lift over

dbSNP: rs796883107; hg19: chr16-57662865;