dbSNP rs3626: PCNA:c.*158G>C (chr20-5115125-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182649.2(PCNA):c.*158G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 557,836 control chromosomes in the GnomAD database, including 4,984 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 ( 2435 hom., cov: 33)

Exomes 𝑓: 0.10 ( 2549 hom. )

Consequence

PCNA
NM_182649.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.508

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

ataxia-telangiectasia-like disorder 2
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

PCNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNA	NM_182649.2 link	c.*158G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000379143.10	NP_872590.1
PCNA	NM_002592.2 link	c.*158G>C		3_prime_UTR_variant	Exon 7 of 7		NP_002583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10 link	c.*158G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_182649.2	ENSP00000368438.5
PCNA	ENST00000379160.3 link	c.*158G>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000368458.3

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23099

AN:

151948

Hom.:

2431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0562

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.100

AC:

40670

AN:

405770

Hom.:

2549

Cov.:

AF XY:

0.0972

AC XY:

20858

AN XY:

214540

show subpopulations

African (AFR)

AF:

0.297

AC:

3312

AN:

11166

American (AMR)

AF:

0.0901

AC:

1275

AN:

14148

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

1851

AN:

12302

East Asian (EAS)

AF:

0.0000705

AC:

AN:

28380

South Asian (SAS)

AF:

0.0633

AC:

2352

AN:

37156

European-Finnish (FIN)

AF:

0.0690

AC:

2053

AN:

29744

Middle Eastern (MID)

AF:

0.142

AC:

253

AN:

1782

European-Non Finnish (NFE)

AF:

0.108

AC:

26842

AN:

247766

Other (OTH)

AF:

0.117

AC:

2730

AN:

23326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1659

3317

4976

6634

8293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23128

AN:

152066

Hom.:

2435

Cov.:

AF XY:

0.149

AC XY:

11046

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.295

AC:

12230

AN:

41456

American (AMR)

AF:

0.108

AC:

1646

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

512

AN:

3468

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0564

AC:

272

AN:

4822

European-Finnish (FIN)

AF:

0.0598

AC:

632

AN:

10560

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7357

AN:

67986

Other (OTH)

AF:

0.150

AC:

316

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

950

1900

2849

3799

4749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.135

Hom.:

241

Bravo

AF:

0.161

Asia WGS

AF:

0.0440

AC:

154

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

(source)

DANN

Benign

0.63

PhyloP100

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over