rs1059234

Positions:

• chr6-36685820-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-36685820-C-T is Benign according to our data. Variant chr6-36685820-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1A	NM_000389.5	c.*20C>T		3_prime_UTR_variant	3/3	ENST00000244741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1A	ENST00000244741.10	c.*20C>T		3_prime_UTR_variant	3/3	1	NM_000389.5	P1

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

GnomAD3 exomes AF: 0.147 AC: 36977 AN: 251332 Hom.: 5241 AF XY: 0.135 AC XY: 18314 AN XY: 135856

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 SAS exome AF: 0.0998

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

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.0827

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0567

Gnomad4 NFE exome AF: 0.0646

Gnomad4 OTH exome AF: 0.106

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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0996 Hom.: 397

Bravo AF: 0.152

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.74
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

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