rs3804968

Variant names:

• chr3-7461013-T-C
• rs3804968
• NM_000844.4:c.1376-570T>C

Variant summary

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

The NM_000844.4(GRM7):​c.1376-570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,048 control chromosomes in the GnomAD database, including 14,520 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 0.41 (14520 hom., cov: 33)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.1376-570T>C		intron_variant	Intron 6 of 9	ENST00000357716.9	NP_000835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM7	ENST00000357716.9	c.1376-570T>C		intron_variant	Intron 6 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.1376-570T>C		intron_variant	Intron 6 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61930 AN: 151926 Hom.: 14510 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.408 AC: 61970 AN: 152048 Hom.: 14520 Cov.: 33 AF XY: 0.402 AC XY: 29897 AN XY: 74314

African (AFR) AF: 0.209 AC: 8661 AN: 41482

American (AMR) AF: 0.352 AC: 5382 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1400 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5174

South Asian (SAS) AF: 0.310 AC: 1494 AN: 4824

European-Finnish (FIN) AF: 0.520 AC: 5488 AN: 10546

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37521 AN: 67966

Other (OTH) AF: 0.438 AC: 925 AN: 2110

Alfa AF: 0.501 Hom.: 11700

Bravo AF: 0.389

Asia WGS AF: 0.240 AC: 831 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.64
PhyloP100		-1.1
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: rs3804968; hg19: chr3-7502700;