7-126522618-T-C

Variant names:

• chr7-126522618-T-C
• rs2041167
• NM_000845.3:c.2430+10334A>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.2430+10334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,048 control chromosomes in the GnomAD database, including 13,995 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 0.42 (13995 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.2430+10334A>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.2430+10334A>G		intron_variant	Intron 9 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63752 AN: 151930 Hom.: 13980 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.420 AC: 63804 AN: 152048 Hom.: 13995 Cov.: 32 AF XY: 0.415 AC XY: 30843 AN XY: 74340

African (AFR) AF: 0.551 AC: 22822 AN: 41450

American (AMR) AF: 0.330 AC: 5028 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2556 AN: 5180

South Asian (SAS) AF: 0.463 AC: 2233 AN: 4826

European-Finnish (FIN) AF: 0.279 AC: 2953 AN: 10584

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25656 AN: 67968

Other (OTH) AF: 0.416 AC: 877 AN: 2108

Alfa AF: 0.418 Hom.: 10574

Bravo AF: 0.425

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.026
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: rs2041167; hg19: chr7-126162672;