4-184652158-C-G

Variant names:

• chr4-184652158-C-G
• rs4861629
• NM_152683.4:c.-60+58C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001345891.2(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_001345891.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001345891.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	NM_152683.4	MANE Select	c.-60+58C>G		intron	N/A	NP_689896.1
	PRIMPOL	NM_001345891.2		c.-60+58C>G		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-57+58C>G		intron	N/A	NP_001332821.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.-60+58C>G		intron	N/A	ENSP00000313816.6
	PRIMPOL	ENST00000512834.5	TSL:1	c.-60+58C>G		intron	N/A	ENSP00000425316.1
	PRIMPOL	ENST00000515774.5	TSL:1	c.-208+58C>G		intron	N/A	ENSP00000421913.1

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.795 AC: 35 AN: 44

Other (OTH) AF: 0.500 AC: 5 AN: 10

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

African (AFR) AF: 0.597 AC: 24707 AN: 41388

American (AMR) AF: 0.638 AC: 9714 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2866 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5156

South Asian (SAS) AF: 0.684 AC: 3296 AN: 4816

European-Finnish (FIN) AF: 0.847 AC: 8948 AN: 10564

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56931 AN: 68004

Other (OTH) AF: 0.733 AC: 1547 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.50
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4861629; hg19: chr4-185573312;