rs3749448

chr3-7146429-G-Achr3-7146429-G-T

Variant summary

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

The NM_000844.4(GRM7):c.520-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,562,530 control chromosomes in the GnomAD database, including 35,611 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 0.26 (5766 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29845 hom.)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4	c.520-23G>A		intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9	c.520-23G>A		intron_variant		1	NM_000844.4	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38981 AN: 151836 Hom.: 5760 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.216 AC: 54027 AN: 250512 Hom.: 6450 AF XY: 0.218 AC XY: 29576 AN XY: 135432

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.199 AC: 281016 AN: 1410576 Hom.: 29845 Cov.: 25 AF XY: 0.201 AC XY: 141662 AN XY: 705000

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.257 AC: 39016 AN: 151954 Hom.: 5766 Cov.: 32 AF XY: 0.254 AC XY: 18881 AN XY: 74262

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.253

Alfa AF: 0.200 Hom.: 5758

Bravo AF: 0.265

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.55
Dann	Benign	0.85

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: rs3749448; hg19: chr3-7188116;