3-6957930-A-G

Variant names:

• chr3-6957930-A-G
• rs163326
• NM_000844.4:c.519+96023A>G

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+96023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,096 control chromosomes in the GnomAD database, including 30,506 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 0.63 (30506 hom., cov: 33)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000844.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.519+96023A>G		intron	N/A	NP_000835.1	Q14831-1
	GRM7	NM_181874.3		c.519+96023A>G		intron	N/A	NP_870989.1	Q14831-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.519+96023A>G		intron	N/A	ENSP00000350348.4	Q14831-1
	GRM7	ENST00000389336.8	TSL:1	c.519+96023A>G		intron	N/A	ENSP00000373987.4	Q14831-5
	GRM7	ENST00000389335.7	TSL:1	n.519+96023A>G		intron	N/A	ENSP00000373986.3	Q14831-4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95366 AN: 151978 Hom.: 30476 Cov.: 33

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.628 AC: 95451 AN: 152096 Hom.: 30506 Cov.: 33 AF XY: 0.623 AC XY: 46296 AN XY: 74350

African (AFR) AF: 0.764 AC: 31739 AN: 41518

American (AMR) AF: 0.577 AC: 8812 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3468 AN: 5158

South Asian (SAS) AF: 0.539 AC: 2603 AN: 4830

European-Finnish (FIN) AF: 0.548 AC: 5787 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39230 AN: 67970

Other (OTH) AF: 0.610 AC: 1290 AN: 2114

Alfa AF: 0.593 Hom.: 86093

Bravo AF: 0.634

Asia WGS AF: 0.603 AC: 2095 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.92
DANN	Benign	0.47
PhyloP100		-0.49
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: rs163326; hg19: chr3-6999617;