dbSNP rs13108061: PRIMPOL:c.-59-7G>T (chr4-184657075-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152683.4(PRIMPOL):c.-59-7G>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 0.559 in 1,201,306 control chromosomes in the GnomAD database, including 192,960 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18800 hom., cov: 33)

Exomes 𝑓: 0.57 ( 174160 hom. )

Consequence

PRIMPOL
NM_152683.4 splice_region, intron

Scores

Splicing: ADA: 0.0001474

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.539

Publications

8 publications found

Variant links:

Genes affected

PRIMPOL (HGNC:26575): (primase and DNA directed polymerase) This gene encodes a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis. An allelic variant in this gene is associated with myopia 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

PRIMPOL 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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4 link	c.-59-7G>T		splice_region_variant, intron_variant	Intron 2 of 13	ENST00000314970.11	NP_689896.1	Q96LW4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11 link	c.-59-7G>T		splice_region_variant, intron_variant	Intron 2 of 13	1	NM_152683.4	ENSP00000313816.6		Q96LW4-1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73129

AN:

151922

Hom.:

18801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.481

GnomAD4 exome

AF:

0.571

AC:

598726

AN:

1049266

Hom.:

174160

Cov.:

AF XY:

0.569

AC XY:

294001

AN XY:

517146

show subpopulations

African (AFR)

AF:

0.296

AC:

6497

AN:

21982

American (AMR)

AF:

0.387

AC:

7469

AN:

19316

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

9738

AN:

16828

East Asian (EAS)

AF:

0.332

AC:

10351

AN:

31154

South Asian (SAS)

AF:

0.475

AC:

19422

AN:

40888

European-Finnish (FIN)

AF:

0.583

AC:

23458

AN:

40256

Middle Eastern (MID)

AF:

0.567

AC:

2603

AN:

4590

European-Non Finnish (NFE)

AF:

0.597

AC:

495853

AN:

830950

Other (OTH)

AF:

0.539

AC:

23335

AN:

43302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

11931

23862

35794

47725

59656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14148

28296

42444

56592

70740

<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:

0.481

AC:

73135

AN:

152040

Hom.:

18800

Cov.:

AF XY:

0.478

AC XY:

35541

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.304

AC:

12630

AN:

41488

American (AMR)

AF:

0.444

AC:

6781

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2044

AN:

3466

East Asian (EAS)

AF:

0.292

AC:

1512

AN:

5184

South Asian (SAS)

AF:

0.505

AC:

2435

AN:

4822

European-Finnish (FIN)

AF:

0.588

AC:

6202

AN:

10544

Middle Eastern (MID)

AF:

0.503

AC:

147

AN:

292

European-Non Finnish (NFE)

AF:

0.586

AC:

39830

AN:

67970

Other (OTH)

AF:

0.480

AC:

1011

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1857

3713

5570

7426

9283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.520

Hom.:

11736

Bravo

AF:

0.461

Asia WGS

AF:

0.407

AC:

1414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.0

(source)

DANN

Benign

0.65

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0040

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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