rs779706

Variant names:

• chr3-7482355-G-C
• rs779706
• NM_000844.4:c.1515+20633G>C

Variant summary

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

The NM_000844.4(GRM7):​c.1515+20633G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,962 control chromosomes in the GnomAD database, including 13,788 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 0.40 (13788 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+20633G>C		intron_variant	Intron 7 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+20633G>C		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+20633G>C		intron_variant	Intron 7 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61376 AN: 151842 Hom.: 13757 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.404 AC: 61459 AN: 151962 Hom.: 13788 Cov.: 32 AF XY: 0.403 AC XY: 29901 AN XY: 74256

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.365

Alfa AF: 0.373 Hom.: 1421

Bravo AF: 0.413

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.65

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: rs779706; hg19: chr3-7524042;