rs1059234

Variant names:

• chr6-36685820-C-T
• rs1059234
• NM_000389.5:c.*20C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000389.5(CDKN1A):​c.*20C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,612,546 control chromosomes in the GnomAD database, including 13,162 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 0.13 (1923 hom., cov: 32)
  • Exomes 𝑓: 0.091 (11239 hom.)
• Consequence: CDKN1A NM_000389.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 78 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000389.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	NM_000389.5	MANE Select	c.*20C>T		3_prime_UTR	Exon 3 of 3	NP_000380.1
	CDKN1A	NM_001291549.3		c.*20C>T		3_prime_UTR	Exon 4 of 4	NP_001278478.1
	CDKN1A	NM_001374509.1		c.*20C>T		3_prime_UTR	Exon 4 of 4	NP_001361438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1A	ENST00000244741.10	TSL:1 MANE Select	c.*20C>T		3_prime_UTR	Exon 3 of 3	ENSP00000244741.6
	CDKN1A	ENST00000405375.5	TSL:1	c.*20C>T		3_prime_UTR	Exon 3 of 3	ENSP00000384849.1
	CDKN1A	ENST00000373711.4	TSL:5	c.*20C>T		3_prime_UTR	Exon 4 of 4	ENSP00000362815.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19730 AN: 152136 Hom.: 1922 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.147 AC: 36977 AN: 251332 AF XY: 0.135

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.0813

Gnomad EAS exome AF: 0.481

Gnomad FIN exome AF: 0.0577

Gnomad NFE exome AF: 0.0649

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0907 AC: 132484 AN: 1460290 Hom.: 11239 Cov.: 31 AF XY: 0.0897 AC XY: 65192 AN XY: 726554

African (AFR) AF: 0.185 AC: 6175 AN: 33444

American (AMR) AF: 0.327 AC: 14610 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 2160 AN: 26126

East Asian (EAS) AF: 0.478 AC: 18966 AN: 39682

South Asian (SAS) AF: 0.102 AC: 8753 AN: 86228

European-Finnish (FIN) AF: 0.0567 AC: 3019 AN: 53278

Middle Eastern (MID) AF: 0.116 AC: 668 AN: 5766

European-Non Finnish (NFE) AF: 0.0646 AC: 71726 AN: 1110694

Other (OTH) AF: 0.106 AC: 6407 AN: 60354

GnomAD4 genome AF: 0.130 AC: 19750 AN: 152256 Hom.: 1923 Cov.: 32 AF XY: 0.134 AC XY: 9945 AN XY: 74442

African (AFR) AF: 0.182 AC: 7556 AN: 41542

American (AMR) AF: 0.218 AC: 3331 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2470 AN: 5172

South Asian (SAS) AF: 0.120 AC: 579 AN: 4826

European-Finnish (FIN) AF: 0.0603 AC: 640 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4480 AN: 68024

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.0925 Hom.: 689

Bravo AF: 0.152

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.74
DANN	Benign	0.76
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1059234; hg19: chr6-36653597; COSMIC: COSV55187270; COSMIC: COSV55187270;