rs778189876
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001164507.2(NEB):c.1470C>T(p.Asp490=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,609,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164507.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.1470C>T | p.Asp490= | splice_region_variant, synonymous_variant | 16/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.1470C>T | p.Asp490= | splice_region_variant, synonymous_variant | 16/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.1470C>T | p.Asp490= | splice_region_variant, synonymous_variant | 16/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.1470C>T | p.Asp490= | splice_region_variant, synonymous_variant | 16/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000489048.1 | n.369C>T | splice_region_variant, non_coding_transcript_exon_variant | 4/12 | 1 | ||||
NEB | ENST00000409198.5 | c.1470C>T | p.Asp490= | splice_region_variant, synonymous_variant | 16/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247582Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134346
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1457650Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 725240
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74470
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change affects codon 490 of the NEB mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NEB protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778189876, gnomAD 0.002%). This variant has been observed in individual(s) with nemaline myopathy (PMID: 25214167). ClinVar contains an entry for this variant (Variation ID: 508804). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at