dbSNP rs17240890: ADGRG1:c.1665-41C>A (chr16-57661656-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_201525.4(ADGRG1):c.1665-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000088 in 1,591,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

ADGRG1
NM_201525.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.52

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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
ADGRG1	NM_201525.4	MANE Select	c.1665-41C>A	intron	N/A	NP_958933.1
ADGRG1	NM_001145771.3		c.1683-41C>A	intron	N/A	NP_001139243.1
ADGRG1	NM_001370428.1		c.1683-41C>A	intron	N/A	NP_001357357.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRG1	ENST00000562631.7	TSL:1 MANE Select	c.1665-41C>A	intron	N/A	ENSP00000455351.2
ADGRG1	ENST00000567835.5	TSL:1	c.1683-41C>A	intron	N/A	ENSP00000456794.1
ADGRG1	ENST00000388813.9	TSL:1	c.1665-41C>A	intron	N/A	ENSP00000373465.5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000288

AC:

AN:

208424

AF XY:

0.0000266

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000645

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1439428

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714458

show subpopulations

African (AFR)

AF:

0.000183

AC:

AN:

32856

American (AMR)

AF:

0.00

AC:

AN:

40714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25694

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38408

South Asian (SAS)

AF:

0.00

AC:

AN:

84060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5378

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101724

Other (OTH)

AF:

0.00

AC:

AN:

59534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000460

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

346

Bravo

AF:

0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.012

(source)

DANN

Benign

0.70

PhyloP100

-4.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over