3-7487868-C-T

Variant names:

• chr3-7487868-C-T
• rs9870680
• NM_000844.4:c.1515+26146C>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+26146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,966 control chromosomes in the GnomAD database, including 15,749 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 0.45 (15749 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 24 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 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.1515+26146C>T		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1515+26146C>T		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.1515+26146C>T		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1515+26146C>T		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1515+26146C>T		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68227 AN: 151848 Hom.: 15744 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.449 AC: 68271 AN: 151966 Hom.: 15749 Cov.: 32 AF XY: 0.454 AC XY: 33701 AN XY: 74240

African (AFR) AF: 0.399 AC: 16563 AN: 41490

American (AMR) AF: 0.475 AC: 7246 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1386 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3567 AN: 5118

South Asian (SAS) AF: 0.361 AC: 1737 AN: 4812

European-Finnish (FIN) AF: 0.571 AC: 6033 AN: 10568

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.446 AC: 30312 AN: 67944

Other (OTH) AF: 0.438 AC: 924 AN: 2110

Alfa AF: 0.444 Hom.: 48104

Bravo AF: 0.444

Asia WGS AF: 0.511 AC: 1776 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.29
PhyloP100		-1.2
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: rs9870680; hg19: chr3-7529555;