3-6861688-G-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000844.4(GRM7):c.300G>T(p.Thr100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,614,142 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00028 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00046 ( 6 hom. )
Consequence
GRM7
NM_000844.4 synonymous
NM_000844.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.279
Genes affected
GRM7 (HGNC:4599): (glutamate metabotropic receptor 7) L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
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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=-0.52).
BP6
Variant 3-6861688-G-T is Benign according to our data. Variant chr3-6861688-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.279 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000282 (43/152322) while in subpopulation SAS AF= 0.00828 (40/4830). AF 95% confidence interval is 0.00625. There are 1 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM7 | NM_000844.4 | c.300G>T | p.Thr100= | synonymous_variant | 1/10 | ENST00000357716.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM7 | ENST00000357716.9 | c.300G>T | p.Thr100= | synonymous_variant | 1/10 | 1 | NM_000844.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000964 AC: 242AN: 250936Hom.: 2 AF XY: 0.00122 AC XY: 165AN XY: 135742
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GnomAD4 exome AF: 0.000459 AC: 671AN: 1461820Hom.: 6 Cov.: 38 AF XY: 0.000653 AC XY: 475AN XY: 727196
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GnomAD4 genome AF: 0.000282 AC: 43AN: 152322Hom.: 1 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | GRM7: BP4, BP7 - |
GRM7-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 25, 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at