NM_000845.3:c.2430+160_2430+187delATATATATATATATATATATATATATAT

Variant names:

• chr7-126532764-GATATATATATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+160_2430+187delATATATATATATATATATATATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+160_2430+187delATATATATATATATATATATATATATAT 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 0.38 (8060 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 (EAS) allele frequency at 95% confidence interval = 0.491 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	NM_000845.3	MANE Select	c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron	N/A	NP_001120795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.2430+160_2430+187delATATATATATATATATATATATATATAT		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.*995+160_*995+187delATATATATATATATATATATATATATAT		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 42287 AN: 111270 Hom.: 8067 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.380 AC: 42275 AN: 111296 Hom.: 8060 Cov.: 0 AF XY: 0.383 AC XY: 20089 AN XY: 52472

African (AFR) AF: 0.303 AC: 9171 AN: 30286

American (AMR) AF: 0.346 AC: 3344 AN: 9662

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1184 AN: 2830

East Asian (EAS) AF: 0.509 AC: 1943 AN: 3814

South Asian (SAS) AF: 0.487 AC: 1553 AN: 3188

European-Finnish (FIN) AF: 0.380 AC: 1755 AN: 4620

Middle Eastern (MID) AF: 0.478 AC: 108 AN: 226

European-Non Finnish (NFE) AF: 0.411 AC: 22364 AN: 54432

Other (OTH) AF: 0.390 AC: 604 AN: 1548

Alfa AF: 0.286 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;