3-7361959-C-T

Variant names:

• chr3-7361959-C-T
• rs13080594
• NM_000844.4:c.1034-53064C>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.1034-53064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,704 control chromosomes in the GnomAD database, including 15,272 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 0.45 (15272 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1034-53064C>T		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.1034-53064C>T		intron_variant	Intron 4 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1034-53064C>T		intron_variant	Intron 4 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67719 AN: 151584 Hom.: 15258 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.447 AC: 67770 AN: 151704 Hom.: 15272 Cov.: 32 AF XY: 0.445 AC XY: 32988 AN XY: 74120

African (AFR) AF: 0.485 AC: 20088 AN: 41390

American (AMR) AF: 0.456 AC: 6947 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1531 AN: 3464

East Asian (EAS) AF: 0.569 AC: 2913 AN: 5120

South Asian (SAS) AF: 0.504 AC: 2427 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3981 AN: 10520

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28494 AN: 67856

Other (OTH) AF: 0.432 AC: 910 AN: 2106

Alfa AF: 0.432 Hom.: 25773

Bravo AF: 0.453

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		-0.18
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: rs13080594; hg19: chr3-7403646;