rs6804466

Positions:

• chr3-7138475-C-T

Variant summary

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

The NM_000844.4(GRM7):​c.520-7977C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,598 control chromosomes in the GnomAD database, including 7,635 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 0.31 (7635 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

Genes affected

GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4	c.520-7977C>T		intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9	c.520-7977C>T		intron_variant		1	NM_000844.4	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46223 AN: 151478 Hom.: 7619 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.305 AC: 46291 AN: 151598 Hom.: 7635 Cov.: 32 AF XY: 0.304 AC XY: 22490 AN XY: 74070

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.265

Alfa AF: 0.286 Hom.: 1055

Bravo AF: 0.300

Asia WGS AF: 0.301 AC: 1038 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.73

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: rs6804466; hg19: chr3-7180162;