chr3-7496689-T-G

Variant names:

• chr3-7496689-T-G
• rs1450099
• NM_000844.4:c.1515+34967T>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+34967T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,820 control chromosomes in the GnomAD database, including 27,297 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 0.60 (27297 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+34967T>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+34967T>G		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+34967T>G		intron_variant	Intron 7 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90376 AN: 151704 Hom.: 27263 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.596 AC: 90459 AN: 151820 Hom.: 27297 Cov.: 32 AF XY: 0.605 AC XY: 44847 AN XY: 74182

African (AFR) AF: 0.588 AC: 24340 AN: 41394

American (AMR) AF: 0.603 AC: 9203 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1867 AN: 3466

East Asian (EAS) AF: 0.751 AC: 3867 AN: 5148

South Asian (SAS) AF: 0.549 AC: 2629 AN: 4788

European-Finnish (FIN) AF: 0.737 AC: 7740 AN: 10500

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39022 AN: 67954

Other (OTH) AF: 0.564 AC: 1190 AN: 2110

Alfa AF: 0.586 Hom.: 3367

Bravo AF: 0.587

Asia WGS AF: 0.652 AC: 2260 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.084
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: rs1450099; hg19: chr3-7538376;