7-86719683-C-G

Variant names:

• chr7-86719683-C-G
• rs2189812
• NM_000840.3:c.-140-45323C>G

Variant summary

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

The NM_000840.3(GRM3):​c.-140-45323C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 151,970 control chromosomes in the GnomAD database, including 47,637 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 0.79 (47637 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.-140-45323C>G		intron_variant	Intron 1 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.-140-45323C>G		intron_variant	Intron 1 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.-140-45323C>G		intron_variant	Intron 2 of 6		XP_047276224.1
GRM3	XM_017012073.3	c.-140-45323C>G		intron_variant	Intron 1 of 3		XP_016867562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.-140-45323C>G		intron_variant	Intron 1 of 5	1	NM_000840.3	ENSP00000355316.2

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119431 AN: 151852 Hom.: 47579 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.787 AC: 119547 AN: 151970 Hom.: 47637 Cov.: 32 AF XY: 0.790 AC XY: 58655 AN XY: 74270

African (AFR) AF: 0.890 AC: 36969 AN: 41520

American (AMR) AF: 0.810 AC: 12336 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2707 AN: 3468

East Asian (EAS) AF: 0.932 AC: 4794 AN: 5144

South Asian (SAS) AF: 0.905 AC: 4366 AN: 4822

European-Finnish (FIN) AF: 0.702 AC: 7417 AN: 10568

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48361 AN: 67900

Other (OTH) AF: 0.776 AC: 1636 AN: 2108

Alfa AF: 0.753 Hom.: 5417

Bravo AF: 0.798

Asia WGS AF: 0.907 AC: 3152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.0
DANN	Benign	0.31
PhyloP100		-0.67
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: rs2189812; hg19: chr7-86348999;