rs6782718

Positions:

• chr3-7446089-G-A

Variant summary

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

The ENST00000357716.9(GRM7):​c.1175-6518G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,996 control chromosomes in the GnomAD database, including 10,996 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 0.35 (10996 hom., cov: 32)
• Consequence: GRM7 ENST00000357716.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1175-6518G>A		intron_variant		ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1175-6518G>A		intron_variant		1	NM_000844.4	ENSP00000350348	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53911 AN: 151880 Hom.: 10987 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.355 AC: 53932 AN: 151996 Hom.: 10996 Cov.: 32 AF XY: 0.350 AC XY: 25983 AN XY: 74274

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.0977

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.386

Alfa AF: 0.427 Hom.: 6661

Bravo AF: 0.341

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.15

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: rs6782718; hg19: chr3-7487776;