NM_000844.4:c.736+53390G>A

Variant names:

• chr3-7200058-G-A
• rs1508724
• NM_000844.4:c.736+53390G>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.736+53390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,074 control chromosomes in the GnomAD database, including 16,915 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 0.42 (16915 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 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.736+53390G>A		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.736+53390G>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.736+53390G>A		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.736+53390G>A		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.736+53390G>A		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63699 AN: 151956 Hom.: 16868 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.419 AC: 63795 AN: 152074 Hom.: 16915 Cov.: 32 AF XY: 0.416 AC XY: 30950 AN XY: 74316

African (AFR) AF: 0.762 AC: 31594 AN: 41470

American (AMR) AF: 0.300 AC: 4580 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1009 AN: 5154

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4822

European-Finnish (FIN) AF: 0.274 AC: 2893 AN: 10566

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19913 AN: 68000

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.337 Hom.: 19391

Bravo AF: 0.437

Asia WGS AF: 0.261 AC: 911 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-1.0
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: rs1508724; hg19: chr3-7241745;