rs2299225

Positions:

• chr7-86818264-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000840.3(GRM3):​c.1325-20575T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 152,148 control chromosomes in the GnomAD database, including 75 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 0.024 (75 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM3	NM_000840.3	c.1325-20575T>G		intron_variant		ENST00000361669.7
GRM3	NM_001363522.2	c.1324+31148T>G		intron_variant
GRM3	XM_047420268.1	c.1325-20575T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM3	ENST00000361669.7	c.1325-20575T>G		intron_variant		1	NM_000840.3	P1
GRM3	ENST00000439827.1	c.1324+31148T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3676 AN: 152030 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0235

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

GnomAD4 genome AF: 0.0242 AC: 3683 AN: 152148 Hom.: 75 Cov.: 32 AF XY: 0.0254 AC XY: 1888 AN XY: 74388

Gnomad4 AFR AF: 0.00558

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0274 Hom.: 11

Bravo AF: 0.0239

Asia WGS AF: 0.0510 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.2
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs2299225; hg19: chr7-86447580;