7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATAT

Variant names:

• chr7-126532764-GATATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+166_2430+187delATATATATATATATATATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000845.3(GRM8):​c.2430+166_2430+187delATATATATATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 3 publications found

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]

ENSG00000287568 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.2430+166_2430+187delATATATATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+166_2430+187delATATATATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+166_2430+187delATATATATATATATATATATAT		intron	N/A	NP_001120795.1	O00222-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.2430+166_2430+187delATATATATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+166_2430+187delATATATATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+166_*995+187delATATATATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

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

African (AFR) AF: 0.0579 AC: 1751 AN: 30250

American (AMR) AF: 0.0445 AC: 428 AN: 9612

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 120 AN: 2822

East Asian (EAS) AF: 0.0386 AC: 146 AN: 3782

South Asian (SAS) AF: 0.0179 AC: 57 AN: 3176

European-Finnish (FIN) AF: 0.0158 AC: 73 AN: 4610

Middle Eastern (MID) AF: 0.0398 AC: 9 AN: 226

European-Non Finnish (NFE) AF: 0.0311 AC: 1689 AN: 54260

Other (OTH) AF: 0.0375 AC: 58 AN: 1548

Alfa AF: 0.0166 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs521; hg19: chr7-126172818;