Variant chrX-136344809-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153834.4(ADGRG4):c.1103C>G(p.Pro368Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,094,375 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P368H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 4 hem. )

Consequence

ADGRG4
NM_153834.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.324

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06944218).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG4	NM_153834.4 link	c.1103C>G	p.Pro368Arg	missense_variant	Exon 6 of 26	ENST00000394143.6	NP_722576.3	Q8IZF6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADGRG4	ENST00000394143.6 link	c.1103C>G	p.Pro368Arg	missense_variant	Exon 6 of 26	1	NM_153834.4	ENSP00000377699.1	Q8IZF6-1
ADGRG4	ENST00000394141.1 link	c.488C>G	p.Pro163Arg	missense_variant	Exon 3 of 23	1		ENSP00000377697.1	Q8IZF6-3
ADGRG4	ENST00000370652.5 link	c.1103C>G	p.Pro368Arg	missense_variant	Exon 4 of 24	5		ENSP00000359686.1	Q8IZF6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181345

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66259

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000531

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1094375

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

359963

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

DANN

Benign

0.86

DEOGEN2

Benign

0.012

T;T;.

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.39

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.053

Sift

Uncertain

0.029

D;D;D

Sift4G

Uncertain

0.058

T;T;D

Polyphen

0.40

B;B;P

Vest4

0.19

MutPred

0.17

Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);.;

MVP

0.030

MPC

0.037

ClinPred

0.075

GERP RS

2.1

Varity_R

0.079

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over