chr7-126532764-GATATATATATATATATAT-G

Variant names:

• chr7-126532764-GATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+170_2430+187delATATATATATATATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000845.3(GRM8):​c.2430+170_2430+187delATATATATATATATATAT 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 0.011 (35 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1267/110960) while in subpopulation AFR AF = 0.0272 (823/30234). AF 95% confidence interval is 0.0257. There are 35 homozygotes in GnomAd4. There are 601 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 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+170_2430+187delATATATATATATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+170_2430+187delATATATATATATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+170_2430+187delATATATATATATATATAT		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+170_2430+187delATATATATATATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+170_2430+187delATATATATATATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+170_*995+187delATATATATATATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1266 AN: 110934 Hom.: 35 Cov.: 0

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00145

Gnomad AMR AF: 0.00750

Gnomad ASJ AF: 0.000709

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.00847

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00402

Gnomad OTH AF: 0.0111

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

GnomAD4 genome AF: 0.0114 AC: 1267 AN: 110960 Hom.: 35 Cov.: 0 AF XY: 0.0115 AC XY: 601 AN XY: 52292

African (AFR) AF: 0.0272 AC: 823 AN: 30234

American (AMR) AF: 0.00750 AC: 72 AN: 9604

Ashkenazi Jewish (ASJ) AF: 0.000709 AC: 2 AN: 2822

East Asian (EAS) AF: 0.0148 AC: 56 AN: 3782

South Asian (SAS) AF: 0.00850 AC: 27 AN: 3176

European-Finnish (FIN) AF: 0.0111 AC: 51 AN: 4612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.00402 AC: 218 AN: 54268

Other (OTH) AF: 0.0110 AC: 17 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;