chr4-849718-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005255.4(GAK):c.3891C>T(p.Asp1297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,613,412 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 0.011 ( 39 hom., cov: 33)
Exomes 𝑓: 0.0026 ( 26 hom. )
Consequence
GAK
NM_005255.4 synonymous
NM_005255.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.21
Genes affected
GAK (HGNC:4113): (cyclin G associated kinase) In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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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=-0.63).
BP6
Variant 4-849718-G-A is Benign according to our data. Variant chr4-849718-G-A is described in ClinVar as [Benign]. Clinvar id is 778842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.21 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1734/152274) while in subpopulation AFR AF= 0.0352 (1465/41572). AF 95% confidence interval is 0.0337. There are 39 homozygotes in gnomad4. There are 803 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1734 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAK | NM_005255.4 | c.3891C>T | p.Asp1297= | synonymous_variant | 28/28 | ENST00000314167.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAK | ENST00000314167.9 | c.3891C>T | p.Asp1297= | synonymous_variant | 28/28 | 1 | NM_005255.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0114 AC: 1733AN: 152156Hom.: 39 Cov.: 33
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GnomAD3 exomes AF: 0.00393 AC: 980AN: 249490Hom.: 11 AF XY: 0.00320 AC XY: 432AN XY: 135178
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GnomAD4 exome AF: 0.00262 AC: 3833AN: 1461138Hom.: 26 Cov.: 30 AF XY: 0.00240 AC XY: 1744AN XY: 726844
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GnomAD4 genome AF: 0.0114 AC: 1734AN: 152274Hom.: 39 Cov.: 33 AF XY: 0.0108 AC XY: 803AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2018 | - - |
Computational scores
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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