rs34605630

chr4-184652783-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+683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 150,952 control chromosomes in the GnomAD database, including 27,079 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 0.58 (27079 hom., cov: 28)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-60+683A>G		intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-60+683A>G		intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87129 AN: 150836 Hom.: 27081 Cov.: 28

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.577 AC: 87150 AN: 150952 Hom.: 27079 Cov.: 28 AF XY: 0.573 AC XY: 42254 AN XY: 73696

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.570

Alfa AF: 0.612 Hom.: 4317

Bravo AF: 0.552

Asia WGS AF: 0.364 AC: 1069 AN: 2938

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.3
Dann	Benign	0.73

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: rs34605630; hg19: chr4-185573937;