NM_000389.5:c.-6+1701_-6+1702dupAG

Variant names:

• chr6-36680498-C-CAG
• rs3176333
• NM_000389.5:c.-6+1701_-6+1702dupAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000389.5(CDKN1A):​c.-6+1701_-6+1702dupAG variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
CDKN1A	NM_000389.5	c.-6+1701_-6+1702dupAG		intron_variant	Intron 1 of 2	ENST00000244741.10	NP_000380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000244741.10	c.-6+1701_-6+1702dupAG		intron_variant	Intron 1 of 2	1	NM_000389.5	ENSP00000244741.6

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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.875 AC: 7 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.250 AC: 2 AN: 8

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.467 AC: 43 AN: 92

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.789 AC: 32366 AN: 41016

American (AMR) AF: 0.597 AC: 9095 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1956 AN: 3464

East Asian (EAS) AF: 0.725 AC: 3678 AN: 5076

South Asian (SAS) AF: 0.475 AC: 2268 AN: 4778

European-Finnish (FIN) AF: 0.385 AC: 4011 AN: 10424

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27710 AN: 67760

Other (OTH) AF: 0.577 AC: 1205 AN: 2090

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3176333; hg19: chr6-36648275;