chr3-6924804-G-A

Variant names:

• chr3-6924804-G-A
• rs339015
• NM_000844.4:c.519+62897G>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.519+62897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,042 control chromosomes in the GnomAD database, including 30,422 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 0.62 (30422 hom., cov: 32)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM7	NM_000844.4	c.519+62897G>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.519+62897G>A		intron_variant	Intron 1 of 9	1	NM_000844.4	ENSP00000350348.4
GRM7	ENST00000440923.7	n.519+62897G>A		intron_variant	Intron 1 of 11	2		ENSP00000412329.3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94140 AN: 151922 Hom.: 30379 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.620 AC: 94238 AN: 152042 Hom.: 30422 Cov.: 32 AF XY: 0.613 AC XY: 45577 AN XY: 74318

African (AFR) AF: 0.821 AC: 34099 AN: 41514

American (AMR) AF: 0.558 AC: 8515 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3433 AN: 5168

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4820

European-Finnish (FIN) AF: 0.503 AC: 5314 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37062 AN: 67942

Other (OTH) AF: 0.598 AC: 1262 AN: 2110

Alfa AF: 0.563 Hom.: 41661

Bravo AF: 0.634

Asia WGS AF: 0.576 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.022
DANN	Benign	0.30
PhyloP100		-1.3
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: rs339015; hg19: chr3-6966491;