chr3-7463227-T-C

Variant names:

• chr3-7463227-T-C
• rs3804967
• NM_000844.4:c.1515+1505T>C

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+1505T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,068 control chromosomes in the GnomAD database, including 10,714 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 0.35 (10714 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1515+1505T>C		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+1505T>C		intron_variant	Intron 7 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1515+1505T>C		intron_variant	Intron 7 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52917 AN: 151950 Hom.: 10711 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.348 AC: 52926 AN: 152068 Hom.: 10714 Cov.: 32 AF XY: 0.343 AC XY: 25468 AN XY: 74324

African (AFR) AF: 0.179 AC: 7423 AN: 41514

American (AMR) AF: 0.307 AC: 4700 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3472

East Asian (EAS) AF: 0.0796 AC: 412 AN: 5176

South Asian (SAS) AF: 0.182 AC: 875 AN: 4816

European-Finnish (FIN) AF: 0.445 AC: 4687 AN: 10544

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32290 AN: 67944

Other (OTH) AF: 0.377 AC: 795 AN: 2106

Alfa AF: 0.397 Hom.: 6689

Bravo AF: 0.338

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.016
DANN	Benign	0.51
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: rs3804967; hg19: chr3-7504914;