Variant chr20-5118870-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_182649.2(PCNA):c.222-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,586,834 control chromosomes in the GnomAD database, including 11,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2422 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9461 hom. )

Consequence

PCNA
NM_182649.2 splice_region, intron

Scores

Splicing: ADA: 0.000007966

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.17

Variant links:

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]

PCNA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-5118870-G-A is Benign according to our data. Variant chr20-5118870-G-A is described in ClinVar as [Benign]. Clinvar id is 3060300.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNA	NM_182649.2 linkuse as main transcript	c.222-4C>T		splice_region_variant, intron_variant		ENST00000379143.10	NP_872590.1	P12004
PCNA	NM_002592.2 linkuse as main transcript	c.222-4C>T		splice_region_variant, intron_variant			NP_002583.1	P12004

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10 linkuse as main transcript	c.222-4C>T		splice_region_variant, intron_variant		1	NM_182649.2	ENSP00000368438.5		P12004
PCNA	ENST00000379160.3 linkuse as main transcript	c.222-4C>T		splice_region_variant, intron_variant		5		ENSP00000368458.3		P12004

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23007

AN:

151922

Hom.:

2418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0559

Gnomad FIN

AF:

0.0595

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.0982

AC:

24616

AN:

250734

Hom.:

1739

AF XY:

0.0948

AC XY:

12853

AN XY:

135556

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.0655

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0580

Gnomad FIN exome

AF:

0.0654

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.107

AC:

153689

AN:

1434794

Hom.:

9461

Cov.:

AF XY:

0.105

AC XY:

75130

AN XY:

713208

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.0706

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0623

Gnomad4 FIN exome

AF:

0.0685

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.152

AC:

23036

AN:

152040

Hom.:

2422

Cov.:

AF XY:

0.148

AC XY:

11006

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0562

Gnomad4 FIN

AF:

0.0595

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.122

Hom.:

1243

Bravo

AF:

0.161

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.117

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PCNA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000080

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over