20-5118990-G-A

Position:

• chr20-5118990-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182649.2(PCNA):​c.222-124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 667,062 control chromosomes in the GnomAD database, including 60,737 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 0.41 (13226 hom., cov: 31)
  • Exomes 𝑓: 0.42 (47511 hom.)
• Consequence: PCNA NM_182649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

Genes affected

PCNA (HGNC:8729): (proliferating cell nuclear antigen) The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNA	NM_182649.2	c.222-124C>T		intron_variant		ENST00000379143.10
PCNA	NM_002592.2	c.222-124C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNA	ENST00000379143.10	c.222-124C>T		intron_variant		1	NM_182649.2	P1
PCNA	ENST00000379160.3	c.222-124C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62587 AN: 151718 Hom.: 13216 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.421 AC: 216872 AN: 515226 Hom.: 47511 AF XY: 0.433 AC XY: 118762 AN XY: 274104

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.413 AC: 62643 AN: 151836 Hom.: 13226 Cov.: 31 AF XY: 0.411 AC XY: 30479 AN XY: 74208

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.412

Alfa AF: 0.418 Hom.: 13057

Bravo AF: 0.405

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs25406; hg19: chr20-5099636; COSMIC: COSV64770469; COSMIC: COSV64770469;