rs1083801

Positions:

• chr3-7481811-G-A
• chr3-7481811-G-C
• chr3-7481811-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.1515+20089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,174 control chromosomes in the GnomAD database, including 46,591 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 0.78 (46591 hom., cov: 33)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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 (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4	c.1515+20089G>A		intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+20089G>A		intron_variant		1	NM_000844.4	P1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117858 AN: 152056 Hom.: 46523 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.775 AC: 117984 AN: 152174 Hom.: 46591 Cov.: 33 AF XY: 0.773 AC XY: 57454 AN XY: 74364

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.717

Alfa AF: 0.757 Hom.: 7446

Bravo AF: 0.778

Asia WGS AF: 0.664 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.29
DANN	Benign	0.56

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: rs1083801; hg19: chr3-7523498;