chr3-7443468-C-A

Variant names:

• chr3-7443468-C-A
• rs779760
• NM_000844.4:c.1175-9139C>A

Variant summary

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

The NM_000844.4(GRM7):​c.1175-9139C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,906 control chromosomes in the GnomAD database, including 38,245 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 0.71 (38245 hom., cov: 31)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 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.1175-9139C>A		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1175-9139C>A		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.1175-9139C>A		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1175-9139C>A		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1175-9139C>A		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107402 AN: 151784 Hom.: 38206 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.708 AC: 107505 AN: 151906 Hom.: 38245 Cov.: 31 AF XY: 0.704 AC XY: 52293 AN XY: 74240

African (AFR) AF: 0.678 AC: 28086 AN: 41436

American (AMR) AF: 0.728 AC: 11084 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2803 AN: 5170

South Asian (SAS) AF: 0.546 AC: 2631 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7909 AN: 10546

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50536 AN: 67934

Other (OTH) AF: 0.724 AC: 1524 AN: 2106

Alfa AF: 0.720 Hom.: 18976

Bravo AF: 0.709

Asia WGS AF: 0.555 AC: 1924 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		0.79
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: rs779760; hg19: chr3-7485155;