4-184654487-G-A

Position:

• chr4-184654487-G-A

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-60+2387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.47 (11875 hom., cov: 20)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-60+2387G>A		intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-60+2387G>A		intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 55708 AN: 117988 Hom.: 11862 Cov.: 20

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.472 AC: 55757 AN: 118062 Hom.: 11875 Cov.: 20 AF XY: 0.485 AC XY: 27210 AN XY: 56050

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.488

Alfa AF: 0.324 Hom.: 958

Bravo AF: 0.412

Asia WGS AF: 0.523 AC: 1811 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
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: rs2705883; hg19: chr4-185575641;