chr3-7209746-A-G

Variant names:

• chr3-7209746-A-G
• rs6769814
• NM_000844.4:c.736+63078A>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.736+63078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,158 control chromosomes in the GnomAD database, including 6,125 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 0.28 (6125 hom., cov: 33)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 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

ENSG00000308972 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.298 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	NM_000844.4	MANE Select	c.736+63078A>G		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.736+63078A>G		intron	N/A	NP_870989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM7	ENST00000357716.9	TSL:1 MANE Select	c.736+63078A>G		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.736+63078A>G		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.736+63078A>G		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42802 AN: 152040 Hom.: 6129 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.281 AC: 42802 AN: 152158 Hom.: 6125 Cov.: 33 AF XY: 0.281 AC XY: 20883 AN XY: 74384

African (AFR) AF: 0.282 AC: 11728 AN: 41526

American (AMR) AF: 0.231 AC: 3537 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3468

East Asian (EAS) AF: 0.126 AC: 651 AN: 5168

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4820

European-Finnish (FIN) AF: 0.274 AC: 2905 AN: 10590

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20521 AN: 67988

Other (OTH) AF: 0.306 AC: 646 AN: 2108

Alfa AF: 0.295 Hom.: 3861

Bravo AF: 0.278

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.091
DANN	Benign	0.35
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: rs6769814; hg19: chr3-7251433;