7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATAT

Variant names:

• chr7-126532764-GATATATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+164_2430+187delATATATATATATATATATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+164_2430+187delATATATATATATATATATATATAT 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 0.23 (3317 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 (AMR) allele frequency at 95% confidence interval = 0.227 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+164_2430+187delATATATATATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+164_2430+187delATATATATATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+164_2430+187delATATATATATATATATATATATAT		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+164_2430+187delATATATATATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+164_2430+187delATATATATATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+164_*995+187delATATATATATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 25195 AN: 111004 Hom.: 3316 Cov.: 0

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.227 AC: 25195 AN: 111030 Hom.: 3317 Cov.: 0 AF XY: 0.230 AC XY: 12058 AN XY: 52332

African (AFR) AF: 0.218 AC: 6603 AN: 30252

American (AMR) AF: 0.235 AC: 2265 AN: 9626

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 554 AN: 2820

East Asian (EAS) AF: 0.136 AC: 515 AN: 3790

South Asian (SAS) AF: 0.176 AC: 559 AN: 3176

European-Finnish (FIN) AF: 0.382 AC: 1760 AN: 4612

Middle Eastern (MID) AF: 0.177 AC: 40 AN: 226

European-Non Finnish (NFE) AF: 0.228 AC: 12386 AN: 54294

Other (OTH) AF: 0.220 AC: 339 AN: 1544

Alfa AF: 0.224 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 (auto)

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;