rs1508722

Variant names:

• chr3-7341140-T-C
• rs1508722
• NM_000844.4:c.1033+34488T>C

Variant summary

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

The NM_181874.3(GRM7):​c.1033+34488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,976 control chromosomes in the GnomAD database, including 12,239 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 0.40 (12239 hom., cov: 32)
• Consequence: GRM7 NM_181874.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181874.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.1033+34488T>C		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1033+34488T>C		intron	N/A	NP_870989.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.1033+34488T>C		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1033+34488T>C		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1033+34488T>C		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60483 AN: 151858 Hom.: 12237 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.398 AC: 60518 AN: 151976 Hom.: 12239 Cov.: 32 AF XY: 0.394 AC XY: 29278 AN XY: 74284

African (AFR) AF: 0.406 AC: 16826 AN: 41452

American (AMR) AF: 0.405 AC: 6174 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1951 AN: 5158

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4816

European-Finnish (FIN) AF: 0.356 AC: 3759 AN: 10570

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27244 AN: 67944

Other (OTH) AF: 0.373 AC: 789 AN: 2114

Alfa AF: 0.399 Hom.: 16601

Bravo AF: 0.398

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.65
PhyloP100		-0.23
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: rs1508722; hg19: chr3-7382827;