rs4074785
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_058195.4(CDKN2A):c.194-10376C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,486 control chromosomes in the GnomAD database, including 1,335 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.12 ( 1335 hom., cov: 27)
Consequence
CDKN2A
NM_058195.4 intron
NM_058195.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.319
Genes affected
CDKN2A (HGNC:1787): (cyclin dependent kinase inhibitor 2A) This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.194-10376C>T | intron_variant | ENST00000579755.2 | |||
LOC124902130 | XR_007061436.1 | n.11040C>T | non_coding_transcript_exon_variant | 2/2 | |||
CDKN2A | NM_001363763.2 | c.-3-10376C>T | intron_variant | ||||
CDKN2A | XM_047422597.1 | c.-3-10376C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.194-10376C>T | intron_variant | 1 | NM_058195.4 | ||||
CDKN2A | ENST00000494262.5 | c.-3-10376C>T | intron_variant | 3 | |||||
CDKN2A | ENST00000498628.6 | c.-3-10376C>T | intron_variant | 2 | |||||
CDKN2A | ENST00000530628.2 | c.194-10376C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.118 AC: 17926AN: 151388Hom.: 1337 Cov.: 27
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.118 AC: 17932AN: 151486Hom.: 1335 Cov.: 27 AF XY: 0.122 AC XY: 9022AN XY: 73956
GnomAD4 genome
?
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27
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9022
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535
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3478
ClinVar
Not reported inComputational scores
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Name
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Prediction
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