dbSNP rs17352: PCNA:c.582+140A>C (chr20-5117330-T-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.63

Publications

7 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=-0.95).

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 rank	MANE	Protein	UniProt
PCNA	NM_182649.2 link	c.582+140A>C		intron_variant	Intron 4 of 5	ENST00000379143.10	NP_872590.1	P12004
PCNA	NM_002592.2 link	c.582+140A>C		intron_variant	Intron 5 of 6		NP_002583.1	P12004

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10 link	c.582+140A>C		intron_variant	Intron 4 of 5	1	NM_182649.2	ENSP00000368438.5		P12004
PCNA	ENST00000379160.3 link	c.582+140A>C		intron_variant	Intron 5 of 6	5		ENSP00000368458.3		P12004

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34633

AN:

152072

Hom.:

7110

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.562

AC:

7148

AN:

12724

American (AMR)

AF:

0.105

AC:

1864

AN:

17680

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

2198

AN:

13818

East Asian (EAS)

AF:

0.000289

AC:

AN:

31112

South Asian (SAS)

AF:

0.0769

AC:

3421

AN:

44468

European-Finnish (FIN)

AF:

0.0691

AC:

2700

AN:

39094

Middle Eastern (MID)

AF:

0.151

AC:

308

AN:

2040

European-Non Finnish (NFE)

AF:

0.110

AC:

32862

AN:

299054

Other (OTH)

AF:

0.140

AC:

3778

AN:

26954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2199

4397

6596

8794

10993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.228

AC:

34714

AN:

152190

Hom.:

7143

Cov.:

AF XY:

0.222

AC XY:

16524

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.555

AC:

23015

AN:

41454

American (AMR)

AF:

0.138

AC:

2112

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

539

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5192

South Asian (SAS)

AF:

0.0706

AC:

341

AN:

4828

European-Finnish (FIN)

AF:

0.0596

AC:

633

AN:

10618

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7462

AN:

68026

Other (OTH)

AF:

0.209

AC:

441

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1073

2146

3218

4291

5364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.167

Hom.:

1287

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

(source)

DANN

Benign

0.41

PhyloP100

-3.6

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