rs1291112487

Variant names:

• chrX-136344382-AT-A
• rs1291112487
• NM_153834.4:c.686-3delT

Your query was ambiguous. Multiple possible variants found:

• chrX-136344382-AT-A
• chrX-136344382-AT-ATT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_153834.4(ADGRG4):​c.686-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,000,111 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000050 (0 hom. 1 hem.)
• Consequence: ADGRG4 NM_153834.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153834.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG4	NM_153834.4	MANE Select	c.686-3delT		splice_region intron	N/A	NP_722576.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRG4	ENST00000394143.6	TSL:1 MANE Select	c.686-9delT		intron	N/A	ENSP00000377699.1	Q8IZF6-1
	ADGRG4	ENST00000394141.1	TSL:1	c.71-9delT		intron	N/A	ENSP00000377697.1	Q8IZF6-3
	ADGRG4	ENST00000370652.5	TSL:5	c.686-9delT		intron	N/A	ENSP00000359686.1	Q8IZF6-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000500 AC: 5 AN: 1000111 Hom.: 0 Cov.: 20 AF XY: 0.00000331 AC XY: 1 AN XY: 301979

African (AFR) AF: 0.00 AC: 0 AN: 23146

American (AMR) AF: 0.00 AC: 0 AN: 23843

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15911

East Asian (EAS) AF: 0.00 AC: 0 AN: 29087

South Asian (SAS) AF: 0.00 AC: 0 AN: 42388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3609

European-Non Finnish (NFE) AF: 0.00000640 AC: 5 AN: 781682

Other (OTH) AF: 0.00 AC: 0 AN: 42183

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1291112487; hg19: chrX-135426541;