rs13353402

Variant names:

• chr3-7424591-G-A
• rs13353402
• NM_000844.4:c.1174+9428G>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.1174+9428G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,144 control chromosomes in the GnomAD database, including 79 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 0.018 (79 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1174+9428G>A		intron_variant	Intron 5 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1174+9428G>A		intron_variant	Intron 5 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1174+9428G>A		intron_variant	Intron 5 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2743 AN: 152026 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0182 AC: 2774 AN: 152144 Hom.: 79 Cov.: 32 AF XY: 0.0173 AC XY: 1290 AN XY: 74386

African (AFR) AF: 0.0567 AC: 2352 AN: 41508

American (AMR) AF: 0.0132 AC: 202 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67992

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.0156 Hom.: 21

Bravo AF: 0.0208

Asia WGS AF: 0.0150 AC: 51 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.36
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: rs13353402; hg19: chr3-7466278;