NM_001100.4:c.808+13C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_001100.4(ACTA1):c.808+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,604,356 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 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
ACTA1
NM_001100.4 intron
NM_001100.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.110
Genes affected
ACTA1 (HGNC:129): (actin alpha 1, skeletal muscle) The product encoded by this gene belongs to the actin family of proteins, which are highly conserved proteins that play a role in cell motility, structure and integrity. Alpha, beta and gamma actin isoforms have been identified, with alpha actins being a major constituent of the contractile apparatus, while beta and gamma actins are involved in the regulation of cell motility. This actin is an alpha actin that is found in skeletal muscle. Mutations in this gene cause a variety of myopathies, including nemaline myopathy, congenital myopathy with excess of thin myofilaments, congenital myopathy with cores, and congenital myopathy with fiber-type disproportion, diseases that lead to muscle fiber defects with manifestations such as hypotonia. [provided by RefSeq, Sep 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 1-229431981-G-A is Benign according to our data. Variant chr1-229431981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000324 (47/1452092) while in subpopulation EAS AF= 0.000709 (28/39478). AF 95% confidence interval is 0.000503. There are 0 homozygotes in gnomad4_exome. There are 23 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTA1 | ENST00000366684.7 | c.808+13C>T | intron_variant | Intron 5 of 6 | 1 | NM_001100.4 | ENSP00000355645.3 | |||
ACTA1 | ENST00000366683.4 | c.808+13C>T | intron_variant | Intron 5 of 6 | 5 | ENSP00000355644.4 | ||||
ACTA1 | ENST00000684723.1 | c.673+13C>T | intron_variant | Intron 4 of 5 | ENSP00000508084.1 | |||||
ENSG00000290037 | ENST00000702606.1 | n.*142G>A | downstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000108 AC: 25AN: 231932Hom.: 0 AF XY: 0.000102 AC XY: 13AN XY: 126848
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GnomAD4 exome AF: 0.0000324 AC: 47AN: 1452092Hom.: 0 Cov.: 34 AF XY: 0.0000319 AC XY: 23AN XY: 721534
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Actin accumulation myopathy Benign:1
Feb 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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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