dbSNP rs25406: PCNA:c.222-124C>T (chr20-5118990-G-A) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.331

Publications

23 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=-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 rank	MANE	Protein	UniProt
PCNA	NM_182649.2 link	c.222-124C>T		intron_variant	Intron 1 of 5	ENST00000379143.10	NP_872590.1	P12004
PCNA	NM_002592.2 link	c.222-124C>T		intron_variant	Intron 2 of 6		NP_002583.1	P12004

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10 link	c.222-124C>T		intron_variant	Intron 1 of 5	1	NM_182649.2	ENSP00000368438.5		P12004
PCNA	ENST00000379160.3 link	c.222-124C>T		intron_variant	Intron 2 of 6	5		ENSP00000368458.3		P12004

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62587

AN:

151718

Hom.:

13216

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.434

AC:

6214

AN:

14304

American (AMR)

AF:

0.294

AC:

7001

AN:

23788

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

7123

AN:

14742

East Asian (EAS)

AF:

0.353

AC:

12036

AN:

34076

South Asian (SAS)

AF:

0.628

AC:

32241

AN:

51374

European-Finnish (FIN)

AF:

0.332

AC:

12932

AN:

38920

Middle Eastern (MID)

AF:

0.510

AC:

1881

AN:

3688

European-Non Finnish (NFE)

AF:

0.409

AC:

125235

AN:

305922

Other (OTH)

AF:

0.430

AC:

12209

AN:

28412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6250

12500

18749

24999

31249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

972

1944

2916

3888

4860

<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:

0.413

AC:

62643

AN:

151836

Hom.:

13226

Cov.:

AF XY:

0.411

AC XY:

30479

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.436

AC:

18031

AN:

41352

American (AMR)

AF:

0.333

AC:

5079

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1694

AN:

3466

East Asian (EAS)

AF:

0.371

AC:

1914

AN:

5162

South Asian (SAS)

AF:

0.642

AC:

3089

AN:

4808

European-Finnish (FIN)

AF:

0.334

AC:

3518

AN:

10548

Middle Eastern (MID)

AF:

0.558

AC:

163

AN:

292

European-Non Finnish (NFE)

AF:

0.411

AC:

27913

AN:

67936

Other (OTH)

AF:

0.412

AC:

870

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1792

3584

5375

7167

8959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.416

Hom.:

20363

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

(source)

DANN

Benign

0.83

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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