7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATAT

Position:

• chr7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000845.3(GRM8):​c.2430+160_2430+187delATATATATATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (8060 hom., cov: 0)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

Genes affected

GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

GRM8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron_variant		ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron_variant		5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 42287 AN: 111270 Hom.: 8067 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.380 AC: 42275 AN: 111296 Hom.: 8060 Cov.: 0 AF XY: 0.383 AC XY: 20089 AN XY: 52472

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs521; hg19: chr7-126172818;