7-126532764-GATATATATATATATATATATAT-G

Position:

• chr7-126532764-GATATATATATATATATATATAT-G

Variant summary

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

The NM_000845.3(GRM8):​c.2430+166_2430+187del 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 0.039 (201 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]

LOC101928357 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM8	NM_000845.3	c.2430+166_2430+187del		intron_variant		ENST00000339582.7
LOC101928357	XR_927937.3	n.215-1957_215-1936del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM8	ENST00000339582.7	c.2430+166_2430+187del		intron_variant		5	NM_000845.3	P1

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 4345 AN: 110952 Hom.: 200 Cov.: 0

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0425

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.0179

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0533

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0377

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

GnomAD4 genome AF: 0.0392 AC: 4350 AN: 110978 Hom.: 201 Cov.: 0 AF XY: 0.0383 AC XY: 2003 AN XY: 52304

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0425

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0375

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;