rs7198790

Variant names:

• chr16-57659464-C-T
• rs7198790
• NM_201525.4:c.1338C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-57659464-C-T
• chr16-57659464-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_201525.4(ADGRG1):​c.1338C>T​(p.Ala446Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,613,796 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (71 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: ADGRG1 NM_201525.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.59
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 16-57659464-C-T is Benign according to our data. Variant chr16-57659464-C-T is described in ClinVar as Benign. ClinVar VariationId is 158617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 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.1338C>T	p.Ala446Ala	synonymous	Exon 11 of 14	NP_958933.1	Q9Y653-2
	ADGRG1	NM_001145771.3		c.1356C>T	p.Ala452Ala	synonymous	Exon 12 of 15	NP_001139243.1	Q9Y653-1
	ADGRG1	NM_001370428.1		c.1356C>T	p.Ala452Ala	synonymous	Exon 12 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.1338C>T	p.Ala446Ala	synonymous	Exon 11 of 14	ENSP00000455351.2	Q9Y653-2
	ADGRG1	ENST00000567835.5	TSL:1	c.1356C>T	p.Ala452Ala	synonymous	Exon 12 of 15	ENSP00000456794.1	Q9Y653-1
	ADGRG1	ENST00000388813.9	TSL:1	c.1338C>T	p.Ala446Ala	synonymous	Exon 12 of 15	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2396 AN: 152166 Hom.: 71 Cov.: 33

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00422 AC: 1052 AN: 249210 AF XY: 0.00308

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000456

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00165 AC: 2411 AN: 1461514 Hom.: 49 Cov.: 35 AF XY: 0.00144 AC XY: 1049 AN XY: 727082

African (AFR) AF: 0.0524 AC: 1755 AN: 33474

American (AMR) AF: 0.00280 AC: 125 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.000254 AC: 282 AN: 1111906

Other (OTH) AF: 0.00344 AC: 208 AN: 60384

GnomAD4 genome AF: 0.0158 AC: 2408 AN: 152282 Hom.: 71 Cov.: 33 AF XY: 0.0153 AC XY: 1140 AN XY: 74446

African (AFR) AF: 0.0541 AC: 2247 AN: 41548

American (AMR) AF: 0.00719 AC: 110 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68018

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00828 Hom.: 14

Bravo AF: 0.0184

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Bilateral frontoparietal polymicrogyria (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs7198790; hg19: chr16-57693376;