3-7496515-T-G

Variant names:

• chr3-7496515-T-G
• rs1450100
• NM_000844.4:c.1515+34793T>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.1515+34793T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,984 control chromosomes in the GnomAD database, including 28,280 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 0.61 (28280 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+34793T>G		intron_variant	Intron 7 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1515+34793T>G		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+34793T>G		intron_variant	Intron 7 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92036 AN: 151866 Hom.: 28245 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.606 AC: 92121 AN: 151984 Hom.: 28280 Cov.: 32 AF XY: 0.614 AC XY: 45601 AN XY: 74290

African (AFR) AF: 0.624 AC: 25886 AN: 41454

American (AMR) AF: 0.607 AC: 9265 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1862 AN: 3462

East Asian (EAS) AF: 0.745 AC: 3845 AN: 5164

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4820

European-Finnish (FIN) AF: 0.737 AC: 7775 AN: 10552

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39036 AN: 67942

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.577 Hom.: 54397

Bravo AF: 0.599

Asia WGS AF: 0.653 AC: 2269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.43
DANN	Benign	0.85
PhyloP100		-0.80
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: rs1450100; hg19: chr3-7538202;