7-126484999-T-C

Variant names:

• chr7-126484999-T-C
• rs2283064
• NM_000845.3:c.2431-38627A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000845.3(GRM8):​c.2431-38627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,788 control chromosomes in the GnomAD database, including 17,666 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17666 hom., cov: 31)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2431-38627A>G		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.2431-38627A>G		intron_variant	Intron 9 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71130 AN: 151670 Hom.: 17634 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.469 AC: 71203 AN: 151788 Hom.: 17666 Cov.: 31 AF XY: 0.462 AC XY: 34293 AN XY: 74162

African (AFR) AF: 0.643 AC: 26604 AN: 41368

American (AMR) AF: 0.393 AC: 5988 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3466

East Asian (EAS) AF: 0.429 AC: 2201 AN: 5130

South Asian (SAS) AF: 0.483 AC: 2326 AN: 4818

European-Finnish (FIN) AF: 0.302 AC: 3185 AN: 10556

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27879 AN: 67916

Other (OTH) AF: 0.486 AC: 1022 AN: 2104

Alfa AF: 0.433 Hom.: 24759

Bravo AF: 0.481

Asia WGS AF: 0.478 AC: 1661 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.36
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs2283064; hg19: chr7-126125053;