chr7-86798310-G-A

Variant names:

• chr7-86798310-G-A
• rs12704290
• NM_000840.3:c.1324+11194G>A

Variant summary

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

The NM_000840.3(GRM3):​c.1324+11194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 152,164 control chromosomes in the GnomAD database, including 701 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 0.089 (701 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• Publications: 45 publications found

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) L-glutamate is the major excitatory neurotransmitter in the central nervous system and 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 3 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. [provided by RefSeq, Jul 2008]

GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000840.3. 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
	GRM3	NM_000840.3	MANE Select	c.1324+11194G>A		intron	N/A	NP_000831.2
	GRM3	NM_001363522.2		c.1324+11194G>A		intron	N/A	NP_001350451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRM3	ENST00000361669.7	TSL:1 MANE Select	c.1324+11194G>A		intron	N/A	ENSP00000355316.2
	GRM3	ENST00000439827.1	TSL:1	c.1324+11194G>A		intron	N/A	ENSP00000398767.1
	GRM3-AS1	ENST00000418031.2	TSL:3	n.113+3952C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13564 AN: 152046 Hom.: 703 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0891 AC: 13556 AN: 152164 Hom.: 701 Cov.: 32 AF XY: 0.0881 AC XY: 6558 AN XY: 74398

African (AFR) AF: 0.0379 AC: 1573 AN: 41522

American (AMR) AF: 0.0778 AC: 1191 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3468

East Asian (EAS) AF: 0.0685 AC: 353 AN: 5150

South Asian (SAS) AF: 0.0770 AC: 371 AN: 4816

European-Finnish (FIN) AF: 0.0991 AC: 1051 AN: 10604

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8169 AN: 67984

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.112 Hom.: 141

Bravo AF: 0.0842

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.63
PhyloP100		0.23
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: rs12704290; hg19: chr7-86427626;