rs2299227
Variant names:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000840.3(GRM3):c.1325-16183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,218 control chromosomes in the GnomAD database, including 103 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 0.028 ( 103 hom., cov: 32)
Consequence
GRM3
NM_000840.3 intron
NM_000840.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.714
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.028 (4269/152218) while in subpopulation NFE AF= 0.0469 (3186/67996). AF 95% confidence interval is 0.0455. There are 103 homozygotes in gnomad4. There are 1945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 4269 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GRM3 | NM_000840.3 | c.1325-16183G>A | intron_variant | Intron 3 of 5 | ENST00000361669.7 | NP_000831.2 | ||
| GRM3 | NM_001363522.2 | c.1325-27714G>A | intron_variant | Intron 3 of 4 | NP_001350451.1 | |||
| GRM3 | XM_047420268.1 | c.1325-16183G>A | intron_variant | Intron 4 of 6 | XP_047276224.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0281 AC: 4270AN: 152100Hom.: 103 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0280 AC: 4269AN: 152218Hom.: 103 Cov.: 32 AF XY: 0.0261 AC XY: 1945AN XY: 74442
GnomAD4 genome
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32
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1945
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74442
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3478
ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at