chr7-126532764-GATATATATATATATATATAT-G

Variant names:

• chr7-126532764-GATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+168_2430+187delATATATATATATATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+168_2430+187delATATATATATATATATATAT 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 0.024 (117 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 = 0.052 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+168_2430+187delATATATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+168_2430+187delATATATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+168_2430+187delATATATATATATATATATAT		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+168_2430+187delATATATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+168_2430+187delATATATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+168_*995+187delATATATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 2632 AN: 110952 Hom.: 115 Cov.: 0

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0120

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.00816

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.0205

Gnomad NFE AF: 0.00728

Gnomad OTH AF: 0.0247

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

GnomAD4 genome AF: 0.0237 AC: 2634 AN: 110978 Hom.: 117 Cov.: 0 AF XY: 0.0235 AC XY: 1227 AN XY: 52298

African (AFR) AF: 0.0542 AC: 1640 AN: 30248

American (AMR) AF: 0.0304 AC: 292 AN: 9604

Ashkenazi Jewish (ASJ) AF: 0.0120 AC: 34 AN: 2822

East Asian (EAS) AF: 0.0503 AC: 190 AN: 3780

South Asian (SAS) AF: 0.00787 AC: 25 AN: 3176

European-Finnish (FIN) AF: 0.00325 AC: 15 AN: 4614

Middle Eastern (MID) AF: 0.0221 AC: 5 AN: 226

European-Non Finnish (NFE) AF: 0.00728 AC: 395 AN: 54270

Other (OTH) AF: 0.0245 AC: 38 AN: 1548

Alfa AF: 0.00518 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;