3-7496515-T-G

Position:

• chr3-7496515-T-G

Variant summary

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

The ENST00000357716.9(GRM7):​c.1515+34793T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,984 control chromosomes in the GnomAD database, including 28,280 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 0.61 (28280 hom., cov: 32)
• Consequence: GRM7 ENST00000357716.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+34793T>G		intron_variant		ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+34793T>G		intron_variant		1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+34793T>G		intron_variant		2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92036 AN: 151866 Hom.: 28245 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.606 AC: 92121 AN: 151984 Hom.: 28280 Cov.: 32 AF XY: 0.614 AC XY: 45601 AN XY: 74290

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.569

Alfa AF: 0.573 Hom.: 33249

Bravo AF: 0.599

Asia WGS AF: 0.653 AC: 2269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.43
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: rs1450100; hg19: chr3-7538202;