4-184650403-C-T

Position:

• chr4-184650403-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.-138+495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,054 control chromosomes in the GnomAD database, including 7,954 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 0.31 (7954 hom., cov: 33)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757

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]

PRIMPOL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.-138+495C>T		intron_variant		ENST00000314970.11	NP_689896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-138+495C>T		intron_variant		1	NM_152683.4	ENSP00000313816.6

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46664 AN: 151936 Hom.: 7952 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.307 AC: 46687 AN: 152054 Hom.: 7954 Cov.: 33 AF XY: 0.316 AC XY: 23527 AN XY: 74344

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.342

Alfa AF: 0.301 Hom.: 9301

Bravo AF: 0.315

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12108497; hg19: chr4-185571557;