rs17352

chr20-5117330-T-G

Variant summary

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

The NM_182649.2(PCNA):c.582+140A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 639,134 control chromosomes in the GnomAD database, including 11,884 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 0.23 (7143 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4741 hom.)
• Consequence: PCNA NM_182649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.63

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNA	NM_182649.2	c.582+140A>C		intron_variant		ENST00000379143.10
PCNA	NM_002592.2	c.582+140A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNA	ENST00000379143.10	c.582+140A>C		intron_variant		1	NM_182649.2	P1
PCNA	ENST00000379160.3	c.582+140A>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34633 AN: 152072 Hom.: 7110 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.111 AC: 54288 AN: 486944 Hom.: 4741 AF XY: 0.108 AC XY: 27654 AN XY: 256158

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.000289

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.0691

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.228 AC: 34714 AN: 152190 Hom.: 7143 Cov.: 33 AF XY: 0.222 AC XY: 16524 AN XY: 74434

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.209

Alfa AF: 0.164 Hom.: 1054

Bravo AF: 0.248

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.23
Dann	Benign	0.41

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: rs17352; hg19: chr20-5097976;