chr16-57663601-C-A

Variant names:

• chr16-57663601-C-A
• rs74022020
• NM_201525.4:c.*19C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201525.4(ADGRG1):​c.*19C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 1,611,196 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (307 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (304 hom.)
• Consequence: ADGRG1 NM_201525.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.30
• 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000306939 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-57663601-C-A is Benign according to our data. Variant chr16-57663601-C-A is described in ClinVar as Benign. ClinVar VariationId is 259864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 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.*19C>A		3_prime_UTR	Exon 14 of 14	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.*19C>A		3_prime_UTR	Exon 15 of 15	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.*19C>A		3_prime_UTR	Exon 15 of 15	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.*19C>A		3_prime_UTR	Exon 14 of 14	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.*19C>A		3_prime_UTR	Exon 15 of 15	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.*19C>A		3_prime_UTR	Exon 15 of 15	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5247 AN: 152230 Hom.: 308 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.00882 AC: 2193 AN: 248704 AF XY: 0.00648

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000433

Gnomad OTH exome AF: 0.00476

GnomAD4 exome AF: 0.00365 AC: 5322 AN: 1458848 Hom.: 304 Cov.: 34 AF XY: 0.00313 AC XY: 2274 AN XY: 725974

African (AFR) AF: 0.126 AC: 4214 AN: 33468

American (AMR) AF: 0.00530 AC: 237 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50950

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000313 AC: 348 AN: 1111562

Other (OTH) AF: 0.00775 AC: 468 AN: 60352

GnomAD4 genome AF: 0.0345 AC: 5252 AN: 152348 Hom.: 307 Cov.: 33 AF XY: 0.0331 AC XY: 2469 AN XY: 74496

African (AFR) AF: 0.119 AC: 4955 AN: 41564

American (AMR) AF: 0.0131 AC: 201 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68038

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0161 Hom.: 13

Bravo AF: 0.0395

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bilateral frontoparietal polymicrogyria (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.080
DANN	Benign	0.87
PhyloP100		-3.3
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: rs74022020; hg19: chr16-57697513;