rs35106713
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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):āc.561T>Cā(p.Ser187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00961 in 1,613,844 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0084 ( 14 hom., cov: 32)
Exomes š: 0.0097 ( 111 hom. )
Consequence
GRM7
NM_000844.4 synonymous
NM_000844.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.803
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=-0.56).
BP6
?
Variant 3-7146493-T-C is Benign according to our data. Variant chr3-7146493-T-C is described in ClinVar as [Benign]. Clinvar id is 709766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.803 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0084 (1279/152230) while in subpopulation NFE AF= 0.0127 (863/68016). AF 95% confidence interval is 0.012. There are 14 homozygotes in gnomad4. There are 647 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRM7 | NM_000844.4 | c.561T>C | p.Ser187= | synonymous_variant | 2/10 | ENST00000357716.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRM7 | ENST00000357716.9 | c.561T>C | p.Ser187= | synonymous_variant | 2/10 | 1 | NM_000844.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00841 AC: 1280AN: 152112Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.00873 AC: 2194AN: 251262Hom.: 13 AF XY: 0.00858 AC XY: 1165AN XY: 135798
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GnomAD4 exome AF: 0.00974 AC: 14234AN: 1461614Hom.: 111 Cov.: 32 AF XY: 0.00945 AC XY: 6868AN XY: 727112
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GnomAD4 genome ? AF: 0.00840 AC: 1279AN: 152230Hom.: 14 Cov.: 32 AF XY: 0.00869 AC XY: 647AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | GRM7: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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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