7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATAT

Position:

• chr7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000845.3(GRM8):​c.2430+174_2430+187delATATATATATATAT 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 0.0064 (6 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+174_2430+187delATATATATATATAT		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+174_2430+187delATATATATATATAT		intron_variant		5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.00642 AC: 712 AN: 110890 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00646

Gnomad ASJ AF: 0.00851

Gnomad EAS AF: 0.00369

Gnomad SAS AF: 0.00345

Gnomad FIN AF: 0.00630

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.00651

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

GnomAD4 genome AF: 0.00643 AC: 713 AN: 110916 Hom.: 6 Cov.: 0 AF XY: 0.00628 AC XY: 328 AN XY: 52268

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00646

Gnomad4 ASJ AF: 0.00851

Gnomad4 EAS AF: 0.00370

Gnomad4 SAS AF: 0.00346

Gnomad4 FIN AF: 0.00630

Gnomad4 NFE AF: 0.00409

Gnomad4 OTH AF: 0.00647

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;