rs5930931

Variant names:

• chrX-136344809-C-A
• rs5930931
• NM_153834.4:c.1103C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-136344809-C-A
• chrX-136344809-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153834.4(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. 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.

• Frequency:
  • Genomes: 𝑓 0.48 (9309 hom., 15710 hem., cov: 23)
  • Exomes 𝑓: 0.46 (78996 hom. 167374 hem.)
• Consequence: ADGRG4 NM_153834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 29 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADGRG4	NM_153834.4	c.1103C>A	p.Pro368His	missense_variant	Exon 6 of 26	ENST00000394143.6	NP_722576.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG4	ENST00000394143.6	c.1103C>A	p.Pro368His	missense_variant	Exon 6 of 26	1	NM_153834.4	ENSP00000377699.1
ADGRG4	ENST00000394141.1	c.488C>A	p.Pro163His	missense_variant	Exon 3 of 23	1		ENSP00000377697.1
ADGRG4	ENST00000370652.5	c.1103C>A	p.Pro368His	missense_variant	Exon 4 of 24	5		ENSP00000359686.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 53304 AN: 111002 Hom.: 9308 Cov.: 23

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

GnomAD2 exomes AF: 0.442 AC: 80089 AN: 181345 AF XY: 0.443

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 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.: 32 AF XY: 0.465 AC XY: 167374 AN XY: 359915

African (AFR) AF: 0.536 AC: 14100 AN: 26330

American (AMR) AF: 0.417 AC: 14636 AN: 35078

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 9235 AN: 19330

East Asian (EAS) AF: 0.314 AC: 9479 AN: 30169

South Asian (SAS) AF: 0.465 AC: 25073 AN: 53951

European-Finnish (FIN) AF: 0.418 AC: 16885 AN: 40395

Middle Eastern (MID) AF: 0.538 AC: 2217 AN: 4123

European-Non Finnish (NFE) AF: 0.470 AC: 393834 AN: 838701

Other (OTH) AF: 0.467 AC: 21472 AN: 45954

GnomAD4 genome AF: 0.480 AC: 53337 AN: 111057 Hom.: 9309 Cov.: 23 AF XY: 0.471 AC XY: 15710 AN XY: 33343

African (AFR) AF: 0.543 AC: 16587 AN: 30563

American (AMR) AF: 0.472 AC: 4962 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1266 AN: 2641

East Asian (EAS) AF: 0.273 AC: 964 AN: 3525

South Asian (SAS) AF: 0.474 AC: 1245 AN: 2629

European-Finnish (FIN) AF: 0.409 AC: 2437 AN: 5957

Middle Eastern (MID) AF: 0.601 AC: 128 AN: 213

European-Non Finnish (NFE) AF: 0.467 AC: 24685 AN: 52817

Other (OTH) AF: 0.524 AC: 796 AN: 1520

Alfa AF: 0.472 Hom.: 60714

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	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.7
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T;T;.
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.33	.;T;T
MetaRNN	Benign	0.00011	T;T;T
MetaSVM	Benign	-0.93	T
PhyloP100		0.32
PrimateAI	Benign	0.24	T
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	T
GERP RS		2.1
Varity_R		0.095
gMVP		0.10
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5930931; hg19: chrX-135426968; COSMIC: COSV54956149;