rs1965222

chr3-7561507-C-T

Variant summary

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

The NM_000844.4(GRM7):c.1516-16915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 456,316 control chromosomes in the GnomAD database, including 3,098 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 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1869 hom.)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4	c.1516-16915C>T		intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9	c.1516-16915C>T		intron_variant		1	NM_000844.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18629 AN: 151922 Hom.: 1229 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0878

GnomAD3 exomes AF: 0.0940 AC: 12618 AN: 134250 Hom.: 748 AF XY: 0.0895 AC XY: 6542 AN XY: 73122

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0831

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.0747

Gnomad SAS exome AF: 0.0279

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.0845

GnomAD4 exome AF: 0.100 AC: 30421 AN: 304276 Hom.: 1869 Cov.: 0 AF XY: 0.0928 AC XY: 16084 AN XY: 173254

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0814

Gnomad4 ASJ exome AF: 0.0782

Gnomad4 EAS exome AF: 0.0704

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.0982

GnomAD4 genome AF: 0.123 AC: 18631 AN: 152040 Hom.: 1229 Cov.: 32 AF XY: 0.122 AC XY: 9055 AN XY: 74360

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0958

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.0684

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0883

Alfa AF: 0.116 Hom.: 1634

Bravo AF: 0.119

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.55

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: rs1965222; hg19: chr3-7603194;