7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATAT

Position:

• chr7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000845.3(GRM8):​c.2430+170_2430+187delATATATATATATATATAT 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 0.011 (35 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1267/110960) while in subpopulation AFR AF= 0.0272 (823/30234). AF 95% confidence interval is 0.0257. There are 35 homozygotes in gnomad4. There are 601 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+170_2430+187delATATATATATATATATAT		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+170_2430+187delATATATATATATATATAT		intron_variant		5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1266 AN: 110934 Hom.: 35 Cov.: 0

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.00750

Gnomad ASJ AF: 0.000709

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.00847

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00402

Gnomad OTH AF: 0.0111

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

GnomAD4 genome AF: 0.0114 AC: 1267 AN: 110960 Hom.: 35 Cov.: 0 AF XY: 0.0115 AC XY: 601 AN XY: 52292

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00750

Gnomad4 ASJ AF: 0.000709

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.00402

Gnomad4 OTH AF: 0.0110

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;