7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATAT

Position:

• chr7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT 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 0.00035 (2 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 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT		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+152_2430+187delATATATATATATATATATATATATATATATATATAT		intron_variant		5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.000351 AC: 39 AN: 110982 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0000993

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00167

Gnomad ASJ AF: 0.000354

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000433

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.000276

Gnomad OTH AF: 0.000651

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

GnomAD4 genome AF: 0.000351 AC: 39 AN: 111008 Hom.: 2 Cov.: 0 AF XY: 0.000325 AC XY: 17 AN XY: 52314

Gnomad4 AFR AF: 0.0000991

Gnomad4 AMR AF: 0.00167

Gnomad4 ASJ AF: 0.000354

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000433

Gnomad4 NFE AF: 0.000276

Gnomad4 OTH AF: 0.000647

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;