4-184652158-C-G

Variant names:

• chr4-184652158-C-G
• rs4861629
• NM_152683.4:c.-60+58C>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+58C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 151,936 control chromosomes in the GnomAD database, including 41,694 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 0.73 (41694 hom., cov: 31)
  • Exomes 𝑓: 0.76 (21 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.-60+58C>G		intron_variant	Intron 2 of 13	ENST00000314970.11	NP_689896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-60+58C>G		intron_variant	Intron 2 of 13	1	NM_152683.4	ENSP00000313816.6

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110475 AN: 151818 Hom.: 41676 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.738

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.758 AC: 50 AN: 66 Hom.: 21 AF XY: 0.773 AC XY: 34 AN XY: 44

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.728 AC: 110548 AN: 151936 Hom.: 41694 Cov.: 31 AF XY: 0.723 AC XY: 53685 AN XY: 74260

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.733

Alfa AF: 0.751 Hom.: 2802

Bravo AF: 0.705

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs4861629; hg19: chr4-185573312;