16-30902524-C-G
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001330.5(CTF1):āc.591C>Gā(p.Pro197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,496,536 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0015 ( 0 hom., cov: 31)
Exomes š: 0.0021 ( 3 hom. )
Consequence
CTF1
NM_001330.5 synonymous
NM_001330.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.188
Genes affected
CTF1 (HGNC:2499): (cardiotrophin 1) The protein encoded by this gene is a secreted cytokine that induces cardiac myocyte hypertrophy in vitro. It has been shown to bind and activate the ILST/gp130 receoptor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 16-30902524-C-G is Benign according to our data. Variant chr16-30902524-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 44182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.188 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTF1 | NM_001330.5 | c.591C>G | p.Pro197= | synonymous_variant | 3/3 | ENST00000279804.3 | NP_001321.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTF1 | ENST00000279804.3 | c.591C>G | p.Pro197= | synonymous_variant | 3/3 | 1 | NM_001330.5 | ENSP00000279804 | P3 | |
CTF1 | ENST00000395019.3 | c.588C>G | p.Pro196= | synonymous_variant | 3/3 | 1 | ENSP00000378465 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00153 AC: 232AN: 152046Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00208 AC: 214AN: 103072Hom.: 0 AF XY: 0.00204 AC XY: 119AN XY: 58380
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GnomAD4 exome AF: 0.00213 AC: 2866AN: 1344380Hom.: 3 Cov.: 30 AF XY: 0.00212 AC XY: 1402AN XY: 662670
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GnomAD4 genome AF: 0.00152 AC: 232AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.00153 AC XY: 114AN XY: 74386
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 22, 2014 | p.Pro197Pro in exon 3 of CTF1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.9% (28/3168) of Eur opean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs397516652) - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 15, 2018 | Variant summary: CTF1 c.591C>G results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 131558 control chromosomes (gnomAD). The observed variant frequency is approximately 72-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CTF1 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.591C>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant once as uncertain significance and once as likely benign. Based on the evidence outlined above, the variant was classified as benign. - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 04, 2017 | - - |
Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at