rs7635212

Variant names:

• chr3-7286376-A-G
• rs7635212
• NM_000844.4:c.737-12308A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-7286376-A-G
• chr3-7286376-A-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.737-12308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,062 control chromosomes in the GnomAD database, including 10,057 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 0.33 (10057 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.737-12308A>G		intron_variant	Intron 2 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.737-12308A>G		intron_variant	Intron 2 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.737-12308A>G		intron_variant	Intron 2 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50238 AN: 151944 Hom.: 10045 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.331 AC: 50261 AN: 152062 Hom.: 10057 Cov.: 32 AF XY: 0.338 AC XY: 25143 AN XY: 74330

African (AFR) AF: 0.101 AC: 4179 AN: 41532

American (AMR) AF: 0.491 AC: 7491 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1470 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2626 AN: 5166

South Asian (SAS) AF: 0.451 AC: 2177 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4520 AN: 10548

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26618 AN: 67940

Other (OTH) AF: 0.328 AC: 695 AN: 2116

Alfa AF: 0.295 Hom.: 1250

Bravo AF: 0.325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.34
PhyloP100		0.51
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: rs7635212; hg19: chr3-7328063;