rs148773767
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000824.5(GLRB):c.798C>T(p.Val266Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
GLRB
NM_000824.5 synonymous
NM_000824.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0110
Genes affected
GLRB (HGNC:4329): (glycine receptor beta) This gene encodes the beta subunit of the glycine receptor, which is a pentamer composed of alpha and beta subunits. The receptor functions as a neurotransmitter-gated ion channel, which produces hyperpolarization via increased chloride conductance due to the binding of glycine to the receptor. Mutations in this gene cause startle disease, also known as hereditary hyperekplexia or congenital stiff-person syndrome, a disease characterized by muscular rigidity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 4-157143853-C-T is Benign according to our data. Variant chr4-157143853-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 540369.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.011 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLRB | NM_000824.5 | c.798C>T | p.Val266Val | synonymous_variant | 8/10 | ENST00000264428.9 | NP_000815.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLRB | ENST00000264428.9 | c.798C>T | p.Val266Val | synonymous_variant | 8/10 | 1 | NM_000824.5 | ENSP00000264428.4 | ||
GLRB | ENST00000509282.1 | c.798C>T | p.Val266Val | synonymous_variant | 8/10 | 1 | ENSP00000427186.1 | |||
GLRB | ENST00000541722.5 | c.798C>T | p.Val266Val | synonymous_variant | 8/9 | 5 | ENSP00000441873.1 | |||
GLRB | ENST00000512619.5 | c.123-26579C>T | intron_variant | 3 | ENSP00000425433.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251064Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135708
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461506Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727096
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74296
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperekplexia 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at