rs17824908

Variant names:

• chr3-7134565-A-G
• rs17824908
• NM_000844.4:c.520-11887A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-7134565-A-G
• chr3-7134565-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000844.4(GRM7):​c.520-11887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,038 control chromosomes in the GnomAD database, including 3,761 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 0.22 (3761 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.520-11887A>G		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.520-11887A>G		intron	N/A	NP_870989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.520-11887A>G		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.520-11887A>G		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.520-11887A>G		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32756 AN: 151920 Hom.: 3760 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.215 AC: 32764 AN: 152038 Hom.: 3761 Cov.: 32 AF XY: 0.215 AC XY: 15992 AN XY: 74310

African (AFR) AF: 0.161 AC: 6675 AN: 41498

American (AMR) AF: 0.140 AC: 2137 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.186 AC: 961 AN: 5172

South Asian (SAS) AF: 0.217 AC: 1049 AN: 4824

European-Finnish (FIN) AF: 0.312 AC: 3292 AN: 10548

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17181 AN: 67942

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.227 Hom.: 7005

Bravo AF: 0.196

Asia WGS AF: 0.227 AC: 790 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.013
DANN	Benign	0.71
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17824908; hg19: chr3-7176252;