rs769198
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_000845.3(GRM8):c.1464C>T(p.Ile488=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,276 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 12 hom. )
Consequence
GRM8
NM_000845.3 synonymous
NM_000845.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.408
Genes affected
GRM8 (HGNC:4600): (glutamate metabotropic receptor 8) 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. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 7-126609392-G-A is Benign according to our data. Variant chr7-126609392-G-A is described in ClinVar as [Benign]. Clinvar id is 782707.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.408 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 12 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM8 | NM_000845.3 | c.1464C>T | p.Ile488= | synonymous_variant | 8/11 | ENST00000339582.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM8 | ENST00000339582.7 | c.1464C>T | p.Ile488= | synonymous_variant | 8/11 | 5 | NM_000845.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00258 AC: 393AN: 152174Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00356 AC: 894AN: 251368Hom.: 2 AF XY: 0.00327 AC XY: 444AN XY: 135846
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GnomAD4 exome AF: 0.00218 AC: 3191AN: 1460984Hom.: 12 Cov.: 29 AF XY: 0.00209 AC XY: 1521AN XY: 726828
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GnomAD4 genome ? AF: 0.00258 AC: 393AN: 152292Hom.: 1 Cov.: 33 AF XY: 0.00306 AC XY: 228AN XY: 74472
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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