rs4862399

Variant names:

• chr4-184653988-A-G
• rs4862399
• NM_152683.4:c.-60+1888A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	NM_152683.4	MANE Select	c.-60+1888A>G		intron	N/A	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.-60+1888A>G		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-57+1888A>G		intron	N/A	NP_001332821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.-60+1888A>G		intron	N/A	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.-60+1888A>G		intron	N/A	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.-208+1888A>G		intron	N/A	ENSP00000421913.1	A0A5S6SZ32

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

African (AFR) AF: 0.0248 AC: 1030 AN: 41554

American (AMR) AF: 0.141 AC: 2156 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3470

East Asian (EAS) AF: 0.155 AC: 803 AN: 5186

South Asian (SAS) AF: 0.136 AC: 656 AN: 4816

European-Finnish (FIN) AF: 0.132 AC: 1404 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8646 AN: 68022

Other (OTH) AF: 0.102 AC: 216 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4862399; hg19: chr4-185575142;