rs779745

Variant names:

• chr3-7538401-A-C
• rs779745
• NM_000844.4:c.1516-40021A>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.1516-40021A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,024 control chromosomes in the GnomAD database, including 28,794 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 0.61 (28794 hom., cov: 34)
• Consequence: GRM7 NM_000844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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-AS1 (HGNC:40267): (GRM7 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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.1516-40021A>C		intron	N/A	NP_000835.1
	GRM7	NM_181874.3		c.1516-40021A>C		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.1516-40021A>C		intron	N/A	ENSP00000350348.4
	GRM7	ENST00000389336.8	TSL:1	c.1516-40021A>C		intron	N/A	ENSP00000373987.4
	GRM7	ENST00000389335.7	TSL:1	n.1516-40021A>C		intron	N/A	ENSP00000373986.3

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92121 AN: 151904 Hom.: 28746 Cov.: 34

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.607 AC: 92235 AN: 152024 Hom.: 28794 Cov.: 34 AF XY: 0.605 AC XY: 44974 AN XY: 74310

African (AFR) AF: 0.759 AC: 31511 AN: 41490

American (AMR) AF: 0.581 AC: 8876 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2194 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2804 AN: 5146

South Asian (SAS) AF: 0.663 AC: 3194 AN: 4818

European-Finnish (FIN) AF: 0.493 AC: 5212 AN: 10564

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36526 AN: 67950

Other (OTH) AF: 0.595 AC: 1255 AN: 2108

Alfa AF: 0.596 Hom.: 3534

Bravo AF: 0.617

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.50
PhyloP100		-1.2
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: rs779745; hg19: chr3-7580088;