chr7-126532764-GAT-G

Variant names:

• chr7-126532764-GAT-G
• rs521
• NM_000845.3:c.2430+186_2430+187delAT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000845.3(GRM8):​c.2430+186_2430+187delAT 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 0.0027 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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+186_2430+187delAT		intron	N/A	NP_000836.2
	GRM8	NM_001371086.1		c.2430+186_2430+187delAT		intron	N/A	NP_001358015.1
	GRM8	NM_001127323.1		c.2430+186_2430+187delAT		intron	N/A	NP_001120795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM8	ENST00000339582.7	TSL:5 MANE Select	c.2430+186_2430+187delAT		intron	N/A	ENSP00000344173.2
	GRM8	ENST00000358373.8	TSL:1	c.2430+186_2430+187delAT		intron	N/A	ENSP00000351142.3
	GRM8	ENST00000341617.7	TSL:1	n.*995+186_*995+187delAT		intron	N/A	ENSP00000345747.3

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 300 AN: 110376 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00173

Gnomad AMI AF: 0.00293

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00712

Gnomad EAS AF: 0.000527

Gnomad SAS AF: 0.00189

Gnomad FIN AF: 0.00131

Gnomad MID AF: 0.00413

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.00394

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

GnomAD4 genome AF: 0.00272 AC: 300 AN: 110400 Hom.: 0 Cov.: 0 AF XY: 0.00244 AC XY: 127 AN XY: 52008

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

African (AFR) AF: 0.00172 AC: 52 AN: 30154

American (AMR) AF: 0.00263 AC: 25 AN: 9514

Ashkenazi Jewish (ASJ) AF: 0.00712 AC: 20 AN: 2808

East Asian (EAS) AF: 0.000529 AC: 2 AN: 3782

South Asian (SAS) AF: 0.00190 AC: 6 AN: 3164

European-Finnish (FIN) AF: 0.00131 AC: 6 AN: 4584

Middle Eastern (MID) AF: 0.00446 AC: 1 AN: 224

European-Non Finnish (NFE) AF: 0.00334 AC: 180 AN: 53954

Other (OTH) AF: 0.00391 AC: 6 AN: 1534

⚠️ 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

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs521; hg19: chr7-126172818;