X-136356380-G-T

Variant names:

• chrX-136356380-G-T
• rs6633822
• NM_153834.4:c.6927+215G>T

Variant summary

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

The NM_153834.4(ADGRG4):​c.6927+215G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 109,904 control chromosomes in the GnomAD database, including 9,634 homozygotes. There are 15,363 hemizygotes in GnomAD. 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 0.49 (9634 hom., 15363 hem., cov: 22)
• Consequence: ADGRG4 NM_153834.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723
• Publications: 1 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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRG4	NM_153834.4	c.6927+215G>T		intron_variant	Intron 9 of 25	ENST00000394143.6	NP_722576.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRG4	ENST00000394143.6	c.6927+215G>T		intron_variant	Intron 9 of 25	1	NM_153834.4	ENSP00000377699.1
ADGRG4	ENST00000394141.1	c.6312+215G>T		intron_variant	Intron 6 of 22	1		ENSP00000377697.1
ADGRG4	ENST00000370652.5	c.6927+215G>T		intron_variant	Intron 7 of 23	5		ENSP00000359686.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 53685 AN: 109845 Hom.: 9633 Cov.: 22

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.489 AC: 53717 AN: 109904 Hom.: 9634 Cov.: 22 AF XY: 0.477 AC XY: 15363 AN XY: 32216

African (AFR) AF: 0.550 AC: 16593 AN: 30168

American (AMR) AF: 0.473 AC: 4862 AN: 10275

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1294 AN: 2645

East Asian (EAS) AF: 0.381 AC: 1318 AN: 3463

South Asian (SAS) AF: 0.469 AC: 1201 AN: 2563

European-Finnish (FIN) AF: 0.416 AC: 2382 AN: 5730

Middle Eastern (MID) AF: 0.599 AC: 127 AN: 212

European-Non Finnish (NFE) AF: 0.472 AC: 24881 AN: 52691

Other (OTH) AF: 0.535 AC: 797 AN: 1490

Alfa AF: 0.470 Hom.: 4216

Bravo AF: 0.496

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.46
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6633822; hg19: chrX-135438539;