rs58704474
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001101.5(ACTB):c.1023C>T(p.Ile341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,613,878 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 39 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 26 hom. )
Consequence
ACTB
NM_001101.5 synonymous
NM_001101.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.177
Genes affected
ACTB (HGNC:132): (actin beta) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome. [provided by RefSeq, Aug 2017]
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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=-0.74).
BP6
?
Variant 7-5527853-G-A is Benign according to our data. Variant chr7-5527853-G-A is described in ClinVar as [Benign]. Clinvar id is 128263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5527853-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.177 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1591/152092) while in subpopulation AFR AF= 0.0367 (1522/41482). AF 95% confidence interval is 0.0352. There are 39 homozygotes in gnomad4. There are 775 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1591 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTB | NM_001101.5 | c.1023C>T | p.Ile341= | synonymous_variant | 6/6 | ENST00000646664.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTB | ENST00000646664.1 | c.1023C>T | p.Ile341= | synonymous_variant | 6/6 | NM_001101.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0104 AC: 1578AN: 151974Hom.: 38 Cov.: 32
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GnomAD3 exomes AF: 0.00266 AC: 668AN: 251406Hom.: 8 AF XY: 0.00199 AC XY: 271AN XY: 135890
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GnomAD4 exome AF: 0.00105 AC: 1542AN: 1461786Hom.: 26 Cov.: 35 AF XY: 0.000934 AC XY: 679AN XY: 727200
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GnomAD4 genome ? AF: 0.0105 AC: 1591AN: 152092Hom.: 39 Cov.: 32 AF XY: 0.0104 AC XY: 775AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 19, 2015 | 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. - |
Baraitser-Winter syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Developmental malformations-deafness-dystonia syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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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