chr16-57629021-C-A

Variant names:

• chr16-57629021-C-A
• rs4993022
• NM_201525.4:c.-36+219C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 VariationId 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.

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>A		intron	N/A	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.-154+219C>A		intron	N/A	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.-154+9140C>A		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>A		intron	N/A	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.-154+8885C>A		intron	N/A	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.-154+193C>A		intron	N/A	ENSP00000373465.5	Q9Y653-2

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

African (AFR) AF: 0.800 AC: 4244 AN: 5308

American (AMR) AF: 0.634 AC: 213 AN: 336

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 823 AN: 1726

East Asian (EAS) AF: 0.642 AC: 865 AN: 1348

South Asian (SAS) AF: 0.457 AC: 2632 AN: 5764

European-Finnish (FIN) AF: 0.426 AC: 40 AN: 94

Middle Eastern (MID) AF: 0.433 AC: 245 AN: 566

European-Non Finnish (NFE) AF: 0.464 AC: 125045 AN: 269386

Other (OTH) AF: 0.499 AC: 4835 AN: 9682

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

African (AFR) AF: 0.789 AC: 31453 AN: 39860

American (AMR) AF: 0.572 AC: 8578 AN: 14992

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1731 AN: 3406

East Asian (EAS) AF: 0.683 AC: 3430 AN: 5022

South Asian (SAS) AF: 0.514 AC: 2372 AN: 4612

European-Finnish (FIN) AF: 0.449 AC: 4462 AN: 9930

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33098 AN: 66460

Other (OTH) AF: 0.559 AC: 1142 AN: 2044

Alfa AF: 0.341 Hom.: 601

Bravo AF: 0.612

Asia WGS AF: 0.613 AC: 2125 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.32
PhyloP100		-1.6
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV66303273; COSMIC: COSV66303273;