7-126532764-GATATATATATATATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr7-126532764-G-GATATATAT
• rs521
• NM_000845.3:c.2430+180_2430+187dupATATATAT

Variant summary

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

The NM_000845.3(GRM8):​c.2430+180_2430+187dupATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0029 (2 hom., cov: 0)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• 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

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+180_2430+187dupATATATAT		intron	N/A	NP_000836.2	O00222-1
	GRM8	NM_001371086.1		c.2430+180_2430+187dupATATATAT		intron	N/A	NP_001358015.1	A0A9L9PYG5
	GRM8	NM_001127323.1		c.2430+180_2430+187dupATATATAT		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+187_2430+188insATATATAT		intron	N/A	ENSP00000344173.2	O00222-1
	GRM8	ENST00000358373.8	TSL:1	c.2430+187_2430+188insATATATAT		intron	N/A	ENSP00000351142.3	O00222-2
	GRM8	ENST00000341617.7	TSL:1	n.*995+187_*995+188insATATATAT		intron	N/A	ENSP00000345747.3	O00222-3

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 316 AN: 110824 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00240

Gnomad ASJ AF: 0.00426

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.000942

Gnomad FIN AF: 0.000217

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00326

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

GnomAD4 genome AF: 0.00285 AC: 316 AN: 110850 Hom.: 2 Cov.: 0 AF XY: 0.00279 AC XY: 146 AN XY: 52246

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00162 AC: 49 AN: 30242

American (AMR) AF: 0.00240 AC: 23 AN: 9580

Ashkenazi Jewish (ASJ) AF: 0.00426 AC: 12 AN: 2820

East Asian (EAS) AF: 0.00185 AC: 7 AN: 3776

South Asian (SAS) AF: 0.000945 AC: 3 AN: 3174

European-Finnish (FIN) AF: 0.000217 AC: 1 AN: 4614

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

European-Non Finnish (NFE) AF: 0.00391 AC: 212 AN: 54192

Other (OTH) AF: 0.00324 AC: 5 AN: 1542

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34

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;