rs13108061

chr4-184657075-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152683.4(PRIMPOL):c.-59-7G>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001474
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-59-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-59-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73129 AN: 151922 Hom.: 18801 Cov.: 33

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.: 13 AF XY: 0.569 AC XY: 294001 AN XY: 517146

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.481 AC: 73135 AN: 152040 Hom.: 18800 Cov.: 33 AF XY: 0.478 AC XY: 35541 AN XY: 74300

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.480

Alfa AF: 0.507 Hom.: 6875

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
Dann	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs13108061; hg19: chr4-185578229; COSMIC: COSV59249386;