dbSNP rs803191: ADGRG4:c.7777-7133T>C (chrX-136380607-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153834.4(ADGRG4):c.7777-7133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.019 ( 3 hom., 12 hem., cov: 0)

Consequence

ADGRG4
NM_153834.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

1 publications found

Variant links:

Genes affected

ADGRG4 (HGNC:18992): (adhesion G protein-coupled receptor G4) This gene encodes a G-protein coupled receptor belonging to a large family of diverse integral membrane proteins that participate in various physiological functions. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The ligand for this family member is unknown, and it is therefore an orphan receptor. This receptor is known to be expressed in normal enterochromaffin cells and in gastrointestinal neuroendocrine carcinoma cells, and it is therefore considered to be a novel biomarker or target for immunotherapy. [provided by RefSeq, May 2010]

ADGRG4 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ADGRG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG4	NM_153834.4 link	c.7777-7133T>C		intron_variant	Intron 15 of 25	ENST00000394143.6	NP_722576.3	Q8IZF6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRG4	ENST00000394143.6 link	c.7777-7133T>C	intron_variant	Intron 15 of 25	1	NM_153834.4	ENSP00000377699.1	Q8IZF6-1
ADGRG4	ENST00000394141.1 link	c.7162-7133T>C	intron_variant	Intron 12 of 22	1		ENSP00000377697.1	Q8IZF6-3
ADGRG4	ENST00000370652.5 link	c.7777-7133T>C	intron_variant	Intron 13 of 23	5		ENSP00000359686.1	Q8IZF6-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

577

AN:

30191

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00119

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.00607

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.0143

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0191

AC:

577

AN:

30205

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

AN XY:

6741

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0339

AC:

282

AN:

8316

American (AMR)

AF:

0.0120

AC:

AN:

2676

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

838

East Asian (EAS)

AF:

0.0327

AC:

AN:

642

South Asian (SAS)

AF:

0.00607

AC:

AN:

494

European-Finnish (FIN)

AF:

0.00801

AC:

AN:

1123

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0143

AC:

220

AN:

15435

Other (OTH)

AF:

0.0164

AC:

AN:

426

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.0793

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.2

(source)

DANN

Benign

0.17

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over