rs17864092

Variant names:

• chr7-126999550-T-C
• rs17864092
• NM_000845.3:c.728-94867A>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.728-94867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,352 control chromosomes in the GnomAD database, including 1,239 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 0.12 (1239 hom., cov: 32)
• Consequence: GRM8 NM_000845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM8	NM_000845.3	c.728-94867A>G		intron_variant	Intron 3 of 10	ENST00000339582.7	NP_000836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM8	ENST00000339582.7	c.728-94867A>G		intron_variant	Intron 3 of 10	5	NM_000845.3	ENSP00000344173.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18171 AN: 151234 Hom.: 1232 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.120 AC: 18198 AN: 151352 Hom.: 1239 Cov.: 32 AF XY: 0.123 AC XY: 9072 AN XY: 73952

African (AFR) AF: 0.136 AC: 5621 AN: 41352

American (AMR) AF: 0.179 AC: 2706 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 518 AN: 3456

East Asian (EAS) AF: 0.0188 AC: 97 AN: 5150

South Asian (SAS) AF: 0.117 AC: 561 AN: 4808

European-Finnish (FIN) AF: 0.120 AC: 1259 AN: 10516

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7081 AN: 67612

Other (OTH) AF: 0.136 AC: 288 AN: 2116

Alfa AF: 0.108 Hom.: 3080

Bravo AF: 0.127

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-0.63
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: rs17864092; hg19: chr7-126639604;