3-7348890-A-G

Variant names:

• chr3-7348890-A-G
• rs7628504
• NM_000844.4:c.1033+42238A>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.1033+42238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,076 control chromosomes in the GnomAD database, including 3,331 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 0.19 (3331 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1033+42238A>G		intron_variant	Intron 4 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1033+42238A>G		intron_variant	Intron 4 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1033+42238A>G		intron_variant	Intron 4 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28618 AN: 151958 Hom.: 3331 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.188 AC: 28611 AN: 152076 Hom.: 3331 Cov.: 32 AF XY: 0.192 AC XY: 14279 AN XY: 74322

African (AFR) AF: 0.0670 AC: 2784 AN: 41548

American (AMR) AF: 0.236 AC: 3594 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1924 AN: 5156

South Asian (SAS) AF: 0.344 AC: 1656 AN: 4814

European-Finnish (FIN) AF: 0.229 AC: 2424 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15059 AN: 67952

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.209 Hom.: 6290

Bravo AF: 0.179

Asia WGS AF: 0.311 AC: 1082 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.48
PhyloP100		-0.44
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: rs7628504; hg19: chr3-7390577;