chr7-127106530-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000845.3(GRM8):āc.693T>Cā(p.Gly231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,954 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.013 ( 42 hom., cov: 32)
Exomes š: 0.0014 ( 43 hom. )
Consequence
GRM8
NM_000845.3 synonymous
NM_000845.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00800
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 7-127106530-A-G is Benign according to our data. Variant chr7-127106530-A-G is described in ClinVar as [Benign]. Clinvar id is 776257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.008 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (2000/152266) while in subpopulation AFR AF= 0.0451 (1875/41544). AF 95% confidence interval is 0.0434. There are 42 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 42 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM8 | NM_000845.3 | c.693T>C | p.Gly231= | synonymous_variant | 3/11 | ENST00000339582.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM8 | ENST00000339582.7 | c.693T>C | p.Gly231= | synonymous_variant | 3/11 | 5 | NM_000845.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0131 AC: 1999AN: 152148Hom.: 42 Cov.: 32
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GnomAD3 exomes AF: 0.00324 AC: 813AN: 251138Hom.: 22 AF XY: 0.00235 AC XY: 319AN XY: 135732
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GnomAD4 exome AF: 0.00137 AC: 2007AN: 1461688Hom.: 43 Cov.: 31 AF XY: 0.00127 AC XY: 926AN XY: 727168
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GnomAD4 genome AF: 0.0131 AC: 2000AN: 152266Hom.: 42 Cov.: 32 AF XY: 0.0126 AC XY: 939AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
GRM8-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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
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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