7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATAT

Variant names:

• chr7-126532764-GATATATATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+162_2430+187delATATATATATATATATATATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+162_2430+187delATATATATATATATATATATATATAT 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 0.075 (586 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 = 0.112 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+162_2430+187delATATATATATATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+162_2430+187delATATATATATATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+162_2430+187delATATATATATATATATATATATATAT		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+162_2430+187delATATATATATATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+162_2430+187delATATATATATATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+162_*995+187delATATATATATATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.0746 AC: 8282 AN: 110956 Hom.: 584 Cov.: 0

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0492

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0747 AC: 8291 AN: 110982 Hom.: 586 Cov.: 0 AF XY: 0.0757 AC XY: 3960 AN XY: 52292

African (AFR) AF: 0.116 AC: 3498 AN: 30272

American (AMR) AF: 0.0982 AC: 945 AN: 9626

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 137 AN: 2820

East Asian (EAS) AF: 0.0584 AC: 221 AN: 3784

South Asian (SAS) AF: 0.0862 AC: 274 AN: 3180

European-Finnish (FIN) AF: 0.0706 AC: 325 AN: 4606

Middle Eastern (MID) AF: 0.0531 AC: 12 AN: 226

European-Non Finnish (NFE) AF: 0.0504 AC: 2733 AN: 54228

Other (OTH) AF: 0.0761 AC: 118 AN: 1550

Alfa AF: 0.0415 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;