rs4135234
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The 6-36676444-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,310 control chromosomes in the GnomAD database, including 764 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 0.093 ( 763 hom., cov: 32)
Exomes 𝑓: 0.073 ( 1 hom. )
Consequence
CDKN1A
NM_001291549.3 upstream_gene
NM_001291549.3 upstream_gene
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.94
Genes affected
CDKN1A (HGNC:1784): (cyclin dependent kinase inhibitor 1A) This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1A | NM_001220777.2 | upstream_gene_variant | |||||
CDKN1A | NM_001291549.3 | upstream_gene_variant | |||||
CDKN1A | NM_001374509.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1A | ENST00000448526.6 | upstream_gene_variant | 3 | P1 | |||||
CDKN1A | ENST00000615513.4 | upstream_gene_variant | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0930 AC: 14151AN: 152110Hom.: 763 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
14151
AN:
152110
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0732 AC: 6AN: 82Hom.: 1 Cov.: 0 AF XY: 0.0217 AC XY: 1AN XY: 46
GnomAD4 exome
AF:
AC:
6
AN:
82
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
46
Gnomad4 ASJ exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0930 AC: 14154AN: 152228Hom.: 763 Cov.: 32 AF XY: 0.0963 AC XY: 7164AN XY: 74416
GnomAD4 genome
?
AF:
AC:
14154
AN:
152228
Hom.:
Cov.:
32
AF XY:
AC XY:
7164
AN XY:
74416
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
233
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at