Variant rs5930931 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000394143.6(ADGRG4):c.1103C>A(p.Pro368His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,205,088 control chromosomes in the GnomAD database, including 88,305 homozygotes. There are 183,084 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 0.48 ( 9309 hom., 15710 hem., cov: 23)

Exomes 𝑓: 0.46 ( 78996 hom. 167374 hem. )

Consequence

ADGRG4
ENST00000394143.6 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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.132889E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRG4	NM_153834.4 linkuse as main transcript	c.1103C>A	p.Pro368His	missense_variant	6/26	ENST00000394143.6	NP_722576.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRG4	ENST00000394143.6 linkuse as main transcript	c.1103C>A	p.Pro368His	missense_variant	6/26	1	NM_153834.4	ENSP00000377699	P1	Q8IZF6-1
ADGRG4	ENST00000394141.1 linkuse as main transcript	c.488C>A	p.Pro163His	missense_variant	3/23	1		ENSP00000377697		Q8IZF6-3
ADGRG4	ENST00000370652.5 linkuse as main transcript	c.1103C>A	p.Pro368His	missense_variant	4/24	5		ENSP00000359686	P1	Q8IZF6-1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

53304

AN:

111002

Hom.:

9308

Cov.:

AF XY:

0.471

AC XY:

15678

AN XY:

33278

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.397

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.442

AC:

80089

AN:

181345

Hom.:

11473

AF XY:

0.443

AC XY:

29324

AN XY:

66259

show subpopulations

Gnomad AFR exome

AF:

0.544

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.463

AC:

506931

AN:

1094031

Hom.:

78996

Cov.:

AF XY:

0.465

AC XY:

167374

AN XY:

359915

show subpopulations

Gnomad4 AFR exome

AF:

0.536

Gnomad4 AMR exome

AF:

0.417

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.465

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.480

AC:

53337

AN:

111057

Hom.:

9309

Cov.:

AF XY:

0.471

AC XY:

15710

AN XY:

33343

show subpopulations

Gnomad4 AFR

AF:

0.543

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.479

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.474

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.467

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.467

Hom.:

49849

Bravo

AF:

0.484

TwinsUK

AF:

0.466

AC:

1727

ALSPAC

AF:

0.454

AC:

1311

ESP6500AA

AF:

0.543

AC:

2081

ESP6500EA

AF:

0.476

AC:

3200

ExAC

AF:

0.448

AC:

54379

EpiCase

AF:

0.485

EpiControl

AF:

0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.7

DANN

Benign

0.96

DEOGEN2

Benign

0.012

T;T;.

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.33

.;T;T

MetaRNN

Benign

0.00011

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.82

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.085

T;T;T

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.88

P;P;P

Vest4

0.069

MPC

0.046

ClinPred

0.0067

GERP RS

2.1

Varity_R

0.095

gMVP

0.10

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