chr7-126562449-T-C

Variant names:

• chr7-126562449-T-C
• rs10487452
• NM_000845.3:c.1495-28562A>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.1495-28562A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,204 control chromosomes in the GnomAD database, including 1,557 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 0.13 (1557 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.1495-28562A>G		intron_variant	Intron 8 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.1495-28562A>G		intron_variant	Intron 8 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19498 AN: 152086 Hom.: 1560 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.128 AC: 19491 AN: 152204 Hom.: 1557 Cov.: 32 AF XY: 0.130 AC XY: 9697 AN XY: 74406

African (AFR) AF: 0.0328 AC: 1362 AN: 41542

American (AMR) AF: 0.150 AC: 2287 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.149 AC: 775 AN: 5184

South Asian (SAS) AF: 0.173 AC: 833 AN: 4816

European-Finnish (FIN) AF: 0.153 AC: 1624 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11448 AN: 68004

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.156 Hom.: 1382

Bravo AF: 0.121

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		0.31
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: rs10487452; hg19: chr7-126202503;