rs1405937

chr4-184650784-G-C

Variant summary

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

The NM_152683.4(PRIMPOL):c.-138+876G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,084 control chromosomes in the GnomAD database, including 8,315 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 0.29 (8315 hom., cov: 33)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-138+876G>C		intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-138+876G>C		intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43994 AN: 151966 Hom.: 8275 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.290 AC: 44094 AN: 152084 Hom.: 8315 Cov.: 33 AF XY: 0.296 AC XY: 21998 AN XY: 74342

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.263

Alfa AF: 0.225 Hom.: 605

Bravo AF: 0.314

Asia WGS AF: 0.508 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.2
Dann	Benign	0.53

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: rs1405937; hg19: chr4-185571938;