4-184651670-C-T

Position:

• chr4-184651670-C-T

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-137-353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 151,926 control chromosomes in the GnomAD database, including 45,915 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 0.77 (45915 hom., cov: 31)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMPOL	NM_152683.4	c.-137-353C>T		intron_variant		ENST00000314970.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-137-353C>T		intron_variant		1	NM_152683.4	P4

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116791 AN: 151808 Hom.: 45885 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.769 AC: 116870 AN: 151926 Hom.: 45915 Cov.: 31 AF XY: 0.762 AC XY: 56652 AN XY: 74302

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.765

Alfa AF: 0.810 Hom.: 6238

Bravo AF: 0.752

Asia WGS AF: 0.525 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.52

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: rs7699420; hg19: chr4-185572824;