rs3176333

chr6-36680498-C-CAGchr6-36680498-C-CAGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000389.5(CDKN1A):c.-6+1701_-6+1702dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,176 control chromosomes in the GnomAD database, including 24,880 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (24860 hom., cov: 0)
  • Exomes 𝑓: 0.50 (20 hom.)
• Consequence: CDKN1A NM_000389.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1A	NM_000389.5	c.-6+1701_-6+1702dup		intron_variant		ENST00000244741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1A	ENST00000244741.10	c.-6+1701_-6+1702dup		intron_variant		1	NM_000389.5	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82634 AN: 150938 Hom.: 24793 Cov.: 0

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.500 AC: 60 AN: 120 Hom.: 20 Cov.: 0 AF XY: 0.532 AC XY: 50 AN XY: 94

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.467

GnomAD4 genome AF: 0.548 AC: 82763 AN: 151056 Hom.: 24860 Cov.: 0 AF XY: 0.550 AC XY: 40563 AN XY: 73790

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.577

Alfa AF: 0.495 Hom.: 2194

Asia WGS AF: 0.615 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3176333; hg19: chr6-36648275;