rs74022020

Variant names:

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.*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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.30

Publications

0 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), ClinGen, G2P

ADGRG1 links:

ENSG00000306939 (HGNC:):

ENSG00000306939 links:

Genome browser will be placed here

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=-0.81).

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG1	NM_201525.4 link	c.*19C>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000562631.7	NP_958933.1	Q9Y653-2A0A0S2Z517

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG1	ENST00000562631.7 link	c.*19C>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_201525.4	ENSP00000455351.2		Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5247

AN:

152230

Hom.:

308

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00313

AC XY:

2274

AN XY:

725974

show subpopulations

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:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000220

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50950

Middle Eastern (MID)

AF:

0.00607

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000313

AC:

348

AN:

1111562

Other (OTH)

AF:

0.00775

AC:

468

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

248

496

744

992

1240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<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:

0.0345

AC:

5252

AN:

152348

Hom.:

307

Cov.:

AF XY:

0.0331

AC XY:

2469

AN XY:

74496

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68038

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

245

489

734

978

1223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0161

Hom.:

Bravo

AF:

0.0395

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bilateral frontoparietal polymicrogyria

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.080

(source)

DANN

Benign

0.87

PhyloP100

-3.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over