7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATAT

Variant names:

• chr7-126532764-GATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+172_2430+187delATATATATATATATAT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000845.3(GRM8):​c.2430+172_2430+187delATATATATATATATAT 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 0.0036 (4 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 4 gene

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+172_2430+187delATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+172_2430+187delATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+172_2430+187delATATATATATATATAT		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+172_2430+187delATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+172_2430+187delATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+172_*995+187delATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.00356 AC: 395 AN: 110948 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00407

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00319

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.00690

Gnomad FIN AF: 0.000433

Gnomad MID AF: 0.0164

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.00260

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

GnomAD4 genome AF: 0.00356 AC: 395 AN: 110974 Hom.: 4 Cov.: 0 AF XY: 0.00344 AC XY: 180 AN XY: 52300

African (AFR) AF: 0.00407 AC: 123 AN: 30256

American (AMR) AF: 0.00406 AC: 39 AN: 9602

Ashkenazi Jewish (ASJ) AF: 0.00319 AC: 9 AN: 2820

East Asian (EAS) AF: 0.00528 AC: 20 AN: 3786

South Asian (SAS) AF: 0.00692 AC: 22 AN: 3178

European-Finnish (FIN) AF: 0.000433 AC: 2 AN: 4616

Middle Eastern (MID) AF: 0.0133 AC: 3 AN: 226

European-Non Finnish (NFE) AF: 0.00315 AC: 171 AN: 54254

Other (OTH) AF: 0.00323 AC: 5 AN: 1546

Alfa AF: 0.00 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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;