rs4862399

Positions:

• chr4-184653988-A-G

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-60+1888A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,248 control chromosomes in the GnomAD database, including 968 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 0.10 (968 hom., cov: 33)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-60+1888A>G		intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-60+1888A>G		intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15437 AN: 152130 Hom.: 969 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15429 AN: 152248 Hom.: 968 Cov.: 33 AF XY: 0.103 AC XY: 7667 AN XY: 74444

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.102

Alfa AF: 0.108 Hom.: 224

Bravo AF: 0.0992

Asia WGS AF: 0.136 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs4862399; hg19: chr4-185575142;