rs3804940

Positions:

• chr3-7503858-C-A
• chr3-7503858-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.1515+42136C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,006 control chromosomes in the GnomAD database, including 5,422 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 0.25 (5422 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRM7	NM_000844.4	c.1515+42136C>A		intron_variant		ENST00000357716.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+42136C>A		intron_variant		1	NM_000844.4	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37716 AN: 151888 Hom.: 5429 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.248 AC: 37714 AN: 152006 Hom.: 5422 Cov.: 32 AF XY: 0.254 AC XY: 18852 AN XY: 74282

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.278

Alfa AF: 0.149 Hom.: 288

Bravo AF: 0.241

Asia WGS AF: 0.385 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.49

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: rs3804940; hg19: chr3-7545545;