rs2305309

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201525.4(ADGRG1):c.1168-20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,613,080 control chromosomes in the GnomAD database, including 140,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11247 hom., cov: 32)

Exomes 𝑓: 0.42 ( 129079 hom. )

Consequence

ADGRG1
NM_201525.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.45

Publications

10 publications found

Variant links:

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), G2P, ClinGen

ADGRG1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_201525.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-57657353-C-A is Benign according to our data. Variant chr16-57657353-C-A is described in ClinVar as Benign. ClinVar VariationId is 158615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADGRG1	NM_201525.4	MANE Select	c.1168-20C>A	intron	N/A	NP_958933.1	Q9Y653-2
ADGRG1	NM_001145771.3		c.1168-20C>A	intron	N/A	NP_001139243.1	Q9Y653-1
ADGRG1	NM_001370428.1		c.1168-20C>A	intron	N/A	NP_001357357.1	Q9Y653-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.1168-20C>A	intron	N/A	ENSP00000455351.2	Q9Y653-2
ADGRG1	ENST00000567835.5	TSL:1	c.1168-20C>A	intron	N/A	ENSP00000456794.1	Q9Y653-1
ADGRG1	ENST00000388813.9	TSL:1	c.1168-20C>A	intron	N/A	ENSP00000373465.5	Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56145

AN:

152000

Hom.:

11245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.400

GnomAD2 exomes

AF:

0.407

AC:

102187

AN:

250974

AF XY:

0.398

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.530

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.415

AC:

606330

AN:

1460966

Hom.:

129079

Cov.:

AF XY:

0.410

AC XY:

298014

AN XY:

726832

show subpopulations

African (AFR)

AF:

0.209

AC:

6981

AN:

33464

American (AMR)

AF:

0.518

AC:

23165

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

13247

AN:

26112

East Asian (EAS)

AF:

0.314

AC:

12453

AN:

39690

South Asian (SAS)

AF:

0.236

AC:

20346

AN:

86238

European-Finnish (FIN)

AF:

0.460

AC:

24511

AN:

53298

Middle Eastern (MID)

AF:

0.407

AC:

2339

AN:

5750

European-Non Finnish (NFE)

AF:

0.431

AC:

479052

AN:

1111352

Other (OTH)

AF:

0.402

AC:

24236

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

18221

36442

54662

72883

91104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14392

28784

43176

57568

71960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.369

AC:

56165

AN:

152114

Hom.:

11247

Cov.:

AF XY:

0.370

AC XY:

27538

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.212

AC:

8800

AN:

41524

American (AMR)

AF:

0.445

AC:

6802

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1783

AN:

3470

East Asian (EAS)

AF:

0.319

AC:

1646

AN:

5158

South Asian (SAS)

AF:

0.226

AC:

1087

AN:

4812

European-Finnish (FIN)

AF:

0.473

AC:

5002

AN:

10586

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.436

AC:

29598

AN:

67958

Other (OTH)

AF:

0.397

AC:

838

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1771

3542

5313

7084

8855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.390

Hom.:

7092

Bravo

AF:

0.369

Asia WGS

AF:

0.260

AC:

903

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Bilateral frontoparietal polymicrogyria (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.073

(source)

DANN

Benign

0.63

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over