Variant X-136349077-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153834.4(ADGRG4):c.5371T>C(p.Phe1791Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,094,075 control chromosomes in the GnomAD database, including 82,105 homozygotes. There are 170,593 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 10098 hom., 15741 hem., cov: 22)

Exomes 𝑓: 0.47 ( 82105 hom. 170593 hem. )

Failed GnomAD Quality Control

Consequence

ADGRG4
NM_153834.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.794

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7827749E-4).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG4	NM_153834.4 linkuse as main transcript	c.5371T>C	p.Phe1791Leu	missense_variant	6/26	ENST00000394143.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG4	ENST00000394143.6 linkuse as main transcript	c.5371T>C	p.Phe1791Leu	missense_variant	6/26	1	NM_153834.4	P1	Q8IZF6-1
ADGRG4	ENST00000394141.1 linkuse as main transcript	c.4756T>C	p.Phe1586Leu	missense_variant	3/23	1			Q8IZF6-3
ADGRG4	ENST00000370652.5 linkuse as main transcript	c.5371T>C	p.Phe1791Leu	missense_variant	4/24	5		P1	Q8IZF6-1

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

54871

AN:

109966

Hom.:

10097

Cov.:

AF XY:

0.486

AC XY:

15704

AN XY:

32304

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.581

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.540

GnomAD3 exomes

AF:

0.462

AC:

82567

AN:

178694

Hom.:

12338

AF XY:

0.466

AC XY:

29742

AN XY:

63808

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.382

Gnomad SAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.472

AC:

516862

AN:

1094075

Hom.:

82105

Cov.:

AF XY:

0.473

AC XY:

170593

AN XY:

360697

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.485

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.482

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.499

AC:

54909

AN:

110024

Hom.:

10098

Cov.:

AF XY:

0.486

AC XY:

15741

AN XY:

32372

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.387

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.410

Gnomad4 NFE

AF:

0.472

Gnomad4 OTH

AF:

0.540

Alfa

AF:

0.477

Hom.:

32675

Bravo

AF:

0.508

TwinsUK

AF:

0.471

AC:

1748

ALSPAC

AF:

0.461

AC:

1332

ESP6500AA

AF:

0.589

AC:

2257

ESP6500EA

AF:

0.480

AC:

3229

ExAC

AF:

0.466

AC:

56547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-1.0

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.034

DANN

Benign

0.16

DEOGEN2

Benign

0.0027

T;T;.

FATHMM_MKL

Benign

0.0014

MetaRNN

Benign

0.00018

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

1.0

N;N;N

REVEL

Benign

0.0050

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.0040

MutPred

0.083

Gain of glycosylation at T1787 (P = 0.0852);Gain of glycosylation at T1787 (P = 0.0852);.;

MPC

0.038

ClinPred

0.00087

GERP RS

-1.8

Varity_R

0.036

gMVP

0.050

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