rs1468412

Positions:

• chr7-86804135-A-T

Variant summary

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

The NM_000840.3(GRM3):​c.1324+17019A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,976 control chromosomes in the GnomAD database, including 12,764 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 0.38 (12764 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM3	NM_000840.3	c.1324+17019A>T		intron_variant		ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.1324+17019A>T		intron_variant			NP_001350451.1
GRM3	XM_047420268.1	c.1324+17019A>T		intron_variant			XP_047276224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.1324+17019A>T		intron_variant		1	NM_000840.3	ENSP00000355316	P1
GRM3	ENST00000439827.1	c.1324+17019A>T		intron_variant		1		ENSP00000398767

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57652 AN: 151860 Hom.: 12742 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.380 AC: 57714 AN: 151976 Hom.: 12764 Cov.: 32 AF XY: 0.378 AC XY: 28083 AN XY: 74274

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.366

Alfa AF: 0.355 Hom.: 1353

Bravo AF: 0.387

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.48

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: rs1468412; hg19: chr7-86433451;