rs61997063
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001614.5(ACTG1):c.546C>T(p.Gly182=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000223 in 1,613,896 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 4 hom. )
Consequence
ACTG1
NM_001614.5 synonymous
NM_001614.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.59
Genes affected
ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 17-81511444-G-A is Benign according to our data. Variant chr17-81511444-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81511444-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000243 (37/152340) while in subpopulation NFE AF= 0.000323 (22/68028). AF 95% confidence interval is 0.000218. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTG1 | NM_001614.5 | c.546C>T | p.Gly182= | synonymous_variant | 4/6 | ENST00000573283.7 | |
ACTG1 | NM_001199954.3 | c.546C>T | p.Gly182= | synonymous_variant | 4/6 | ||
ACTG1 | NR_037688.3 | n.618C>T | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG1 | ENST00000573283.7 | c.546C>T | p.Gly182= | synonymous_variant | 4/6 | 5 | NM_001614.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000256 AC: 64AN: 250476Hom.: 1 AF XY: 0.000280 AC XY: 38AN XY: 135678
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GnomAD4 exome AF: 0.000221 AC: 323AN: 1461556Hom.: 4 Cov.: 37 AF XY: 0.000232 AC XY: 169AN XY: 727084
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | ACTG1: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 14, 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 25, 2015 | p.Gly182Gly in exon 4 of ACTG1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence. It has been identified in 23/65430 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org;dbSNP rs61997063). - |
Autosomal dominant nonsyndromic hearing loss 20 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Autosomal dominant nonsyndromic hearing loss 20;C3281235:Baraitser-winter syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Baraitser-winter syndrome 2 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
RBP_binding_hub_radar
RBP_regulation_power_radar
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