16-57629021-C-G

Variant names:

• chr16-57629021-C-G
• rs4993022
• NM_201525.4:c.-36+219C>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+219C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 443,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000014 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ADGRG1 NM_201525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	NM_201525.4	MANE Select	c.-36+219C>G		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+219C>G		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9140C>G		intron	N/A	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.-36+219C>G		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8885C>G		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+193C>G		intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147658 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000667

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000169 AC: 5 AN: 296154 Hom.: 0 AF XY: 0.0000143 AC XY: 2 AN XY: 140316

African (AFR) AF: 0.00 AC: 0 AN: 5322

American (AMR) AF: 0.00 AC: 0 AN: 340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1738

East Asian (EAS) AF: 0.00 AC: 0 AN: 1352

South Asian (SAS) AF: 0.00 AC: 0 AN: 5796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 94

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 572

European-Non Finnish (NFE) AF: 0.0000184 AC: 5 AN: 271186

Other (OTH) AF: 0.00 AC: 0 AN: 9754

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147658 Hom.: 0 Cov.: 28 AF XY: 0.0000278 AC XY: 2 AN XY: 71914

African (AFR) AF: 0.0000251 AC: 1 AN: 39820

American (AMR) AF: 0.0000667 AC: 1 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66576

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.22
PhyloP100		-1.6
PromoterAI		-0.015	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: rs4993022; hg19: chr16-57662933;