3-7381807-T-G

Variant names:

• chr3-7381807-T-G
• rs9863764
• NM_000844.4:c.1034-33216T>G

Variant summary

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

The NM_000844.4(GRM7):​c.1034-33216T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,092 control chromosomes in the GnomAD database, including 3,959 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 0.19 (3959 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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.1034-33216T>G		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1034-33216T>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.1034-33216T>G		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1034-33216T>G		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1034-33216T>G		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29620 AN: 151974 Hom.: 3966 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.195 AC: 29637 AN: 152092 Hom.: 3959 Cov.: 32 AF XY: 0.195 AC XY: 14471 AN XY: 74344

African (AFR) AF: 0.370 AC: 15317 AN: 41426

American (AMR) AF: 0.143 AC: 2181 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1762 AN: 5166

South Asian (SAS) AF: 0.159 AC: 769 AN: 4826

European-Finnish (FIN) AF: 0.0752 AC: 798 AN: 10606

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7415 AN: 67982

Other (OTH) AF: 0.197 AC: 417 AN: 2114

Alfa AF: 0.141 Hom.: 3503

Bravo AF: 0.210

Asia WGS AF: 0.237 AC: 823 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		0.038
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: rs9863764; hg19: chr3-7423494;