rs9864350

Variant names:

• chr3-7161222-C-T
• rs9864350
• NM_000844.4:c.736+14554C>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.736+14554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 151,882 control chromosomes in the GnomAD database, including 822 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 0.066 (822 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.736+14554C>T		intron	N/A	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.736+14554C>T		intron	N/A	NP_870989.1	Q14831-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.736+14554C>T		intron	N/A	ENSP00000350348.4	Q14831-1
	GRM7	ENST00000389336.8	TSL:1	c.736+14554C>T		intron	N/A	ENSP00000373987.4	Q14831-5
	GRM7	ENST00000389335.7	TSL:1	n.736+14554C>T		intron	N/A	ENSP00000373986.3	Q14831-4

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9917 AN: 151766 Hom.: 815 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00781

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0655 AC: 9954 AN: 151882 Hom.: 822 Cov.: 31 AF XY: 0.0648 AC XY: 4809 AN XY: 74224

African (AFR) AF: 0.184 AC: 7608 AN: 41360

American (AMR) AF: 0.0649 AC: 991 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.0885 AC: 454 AN: 5130

South Asian (SAS) AF: 0.0334 AC: 160 AN: 4790

European-Finnish (FIN) AF: 0.00340 AC: 36 AN: 10584

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00781 AC: 531 AN: 67972

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0409 Hom.: 69

Bravo AF: 0.0766

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-1.3
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: rs9864350; hg19: chr3-7202909;