chr7-126532764-GATATATATATATATATATAT-G

Position:

• chr7-126532764-GATATATATATATATATATAT-G

Variant summary

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

The NM_000845.3(GRM8):​c.2430+168_2430+187delATATATATATATATATATAT 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 0.024 (117 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 (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+168_2430+187delATATATATATATATATATAT		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+168_2430+187delATATATATATATATATATAT		intron_variant		5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 2632 AN: 110952 Hom.: 115 Cov.: 0

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0120

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.00816

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.0205

Gnomad NFE AF: 0.00728

Gnomad OTH AF: 0.0247

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

GnomAD4 genome AF: 0.0237 AC: 2634 AN: 110978 Hom.: 117 Cov.: 0 AF XY: 0.0235 AC XY: 1227 AN XY: 52298

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0120

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.00325

Gnomad4 NFE AF: 0.00728

Gnomad4 OTH AF: 0.0245

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;