rs25405

Positions:

• chr20-5119342-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182649.2(PCNA):​c.221+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,180 control chromosomes in the GnomAD database, including 2,576 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 0.15 (2576 hom., cov: 33)
• Consequence: PCNA NM_182649.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNA	NM_182649.2	c.221+236A>G		intron_variant		ENST00000379143.10	NP_872590.1
PCNA	NM_002592.2	c.221+236A>G		intron_variant			NP_002583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10	c.221+236A>G		intron_variant		1	NM_182649.2	ENSP00000368438.5
PCNA	ENST00000379160.3	c.221+236A>G		intron_variant		5		ENSP00000368458.3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23531 AN: 152062 Hom.: 2570 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23564 AN: 152180 Hom.: 2576 Cov.: 33 AF XY: 0.151 AC XY: 11236 AN XY: 74408

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.152

Alfa AF: 0.136 Hom.: 244

Bravo AF: 0.164

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.81

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: rs25405; hg19: chr20-5099988;