3-7482355-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181874.3(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_181874.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542
• Publications: 12 publications found

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]

GRM7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181874.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.1515+20633G>C		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1515+20633G>C		intron	N/A	NP_870989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.1515+20633G>C		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1515+20633G>C		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1515+20633G>C		intron	N/A	ENSP00000373986.3

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

African (AFR) AF: 0.611 AC: 25325 AN: 41454

American (AMR) AF: 0.345 AC: 5266 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2128 AN: 5158

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4812

European-Finnish (FIN) AF: 0.345 AC: 3632 AN: 10542

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21364 AN: 67942

Other (OTH) AF: 0.365 AC: 770 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs779706; hg19: chr3-7524042;