rs3804968

Positions:

• chr3-7461013-T-C

Variant summary

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

The NM_000844.4(GRM7):​c.1376-570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,048 control chromosomes in the GnomAD database, including 14,520 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 0.41 (14520 hom., cov: 33)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1376-570T>C		intron_variant		ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1376-570T>C		intron_variant		1	NM_000844.4	ENSP00000350348	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61930 AN: 151926 Hom.: 14510 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.408 AC: 61970 AN: 152048 Hom.: 14520 Cov.: 33 AF XY: 0.402 AC XY: 29897 AN XY: 74314

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.438

Alfa AF: 0.502 Hom.: 10605

Bravo AF: 0.389

Asia WGS AF: 0.240 AC: 831 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.64

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: rs3804968; hg19: chr3-7502700;