7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATAT

Variant names:

• chr7-126532764-GATATATATATATATATATATATATATATATATATAT-G
• rs521
• NM_000845.3:c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT 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 0.00035 (2 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 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT		intron_variant	Intron 9 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.2430+152_2430+187delATATATATATATATATATATATATATATATATATAT		intron_variant	Intron 9 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.000351 AC: 39 AN: 110982 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0000993

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00167

Gnomad ASJ AF: 0.000354

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000433

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.000276

Gnomad OTH AF: 0.000651

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

GnomAD4 genome AF: 0.000351 AC: 39 AN: 111008 Hom.: 2 Cov.: 0 AF XY: 0.000325 AC XY: 17 AN XY: 52314

African (AFR) AF: 0.0000991 AC: 3 AN: 30266

American (AMR) AF: 0.00167 AC: 16 AN: 9604

Ashkenazi Jewish (ASJ) AF: 0.000354 AC: 1 AN: 2822

East Asian (EAS) AF: 0.00 AC: 0 AN: 3786

South Asian (SAS) AF: 0.00 AC: 0 AN: 3178

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

Middle Eastern (MID) AF: 0.00442 AC: 1 AN: 226

European-Non Finnish (NFE) AF: 0.000276 AC: 15 AN: 54274

Other (OTH) AF: 0.000647 AC: 1 AN: 1546

Alfa AF: 0.00 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;