chr3-7519462-G-T

Variant names:

• chr3-7519462-G-T
• rs756084
• NM_000844.4:c.1515+57740G>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.1515+57740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,992 control chromosomes in the GnomAD database, including 30,529 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 0.62 (30529 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 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.1515+57740G>T		intron	N/A	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.1515+57740G>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.1515+57740G>T		intron	N/A	ENSP00000350348.4	Q14831-1
	GRM7	ENST00000389336.8	TSL:1	c.1515+57740G>T		intron	N/A	ENSP00000373987.4	Q14831-5
	GRM7	ENST00000389335.7	TSL:1	n.1515+57740G>T		intron	N/A	ENSP00000373986.3	Q14831-4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94596 AN: 151874 Hom.: 30482 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.623 AC: 94707 AN: 151992 Hom.: 30529 Cov.: 32 AF XY: 0.618 AC XY: 45937 AN XY: 74290

African (AFR) AF: 0.797 AC: 33068 AN: 41472

American (AMR) AF: 0.598 AC: 9128 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2192 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2434 AN: 5172

South Asian (SAS) AF: 0.647 AC: 3118 AN: 4822

European-Finnish (FIN) AF: 0.490 AC: 5155 AN: 10520

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37662 AN: 67952

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.606 Hom.: 20716

Bravo AF: 0.636

Asia WGS AF: 0.574 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.93
DANN	Benign	0.48
PhyloP100		-0.55
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: rs756084; hg19: chr3-7561149;