rs11131063

Variant names:

• chr3-7126014-G-A
• rs11131063
• NM_000844.4:c.520-20438G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000844.4(GRM7):​c.520-20438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,034 control chromosomes in the GnomAD database, including 4,378 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 0.24 (4378 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.520-20438G>A		intron_variant	Intron 1 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.520-20438G>A		intron_variant	Intron 1 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.520-20438G>A		intron_variant	Intron 1 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35808 AN: 151916 Hom.: 4375 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.236 AC: 35825 AN: 152034 Hom.: 4378 Cov.: 32 AF XY: 0.234 AC XY: 17364 AN XY: 74282

African (AFR) AF: 0.219 AC: 9085 AN: 41474

American (AMR) AF: 0.151 AC: 2305 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3470

East Asian (EAS) AF: 0.186 AC: 961 AN: 5166

South Asian (SAS) AF: 0.217 AC: 1042 AN: 4810

European-Finnish (FIN) AF: 0.315 AC: 3321 AN: 10548

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17560 AN: 67976

Other (OTH) AF: 0.208 AC: 439 AN: 2114

Alfa AF: 0.245 Hom.: 14866

Bravo AF: 0.218

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		0.33
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: rs11131063; hg19: chr3-7167701;