rs6465084

Variant names:

• chr7-86774159-A-G
• rs6465084
• NM_000840.3:c.468+8546A>G

Variant summary

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

The NM_000840.3(GRM3):​c.468+8546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,014 control chromosomes in the GnomAD database, including 4,986 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 0.25 (4986 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 47 publications found

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) 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. [provided by RefSeq, Jul 2008]

GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.468+8546A>G		intron_variant	Intron 2 of 5	ENST00000361669.7	NP_000831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.468+8546A>G		intron_variant	Intron 2 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.468+8546A>G		intron_variant	Intron 2 of 4	1		ENSP00000398767.1
GRM3	ENST00000454217.1	c.85-12102A>G		intron_variant	Intron 1 of 1	3		ENSP00000405427.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38636 AN: 151896 Hom.: 4976 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.254 AC: 38664 AN: 152014 Hom.: 4986 Cov.: 32 AF XY: 0.251 AC XY: 18671 AN XY: 74302

African (AFR) AF: 0.302 AC: 12501 AN: 41456

American (AMR) AF: 0.209 AC: 3194 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 982 AN: 3460

East Asian (EAS) AF: 0.130 AC: 675 AN: 5176

South Asian (SAS) AF: 0.204 AC: 986 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2513 AN: 10586

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16891 AN: 67954

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.246 Hom.: 17631

Bravo AF: 0.252

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.071
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: rs6465084; hg19: chr7-86403475;