4-184656316-A-T

Variant names:

• chr4-184656316-A-T
• rs2720382
• NM_152683.4:c.-59-766A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152683.4(PRIMPOL):​c.-59-766A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,004 control chromosomes in the GnomAD database, including 3,901 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 0.19 (3901 hom., cov: 31)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.-59-766A>T		intron_variant	Intron 2 of 13	ENST00000314970.11	NP_689896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-59-766A>T		intron_variant	Intron 2 of 13	1	NM_152683.4	ENSP00000313816.6

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29480 AN: 151884 Hom.: 3899 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.194 AC: 29498 AN: 152004 Hom.: 3901 Cov.: 31 AF XY: 0.201 AC XY: 14910 AN XY: 74290

African (AFR) AF: 0.148 AC: 6135 AN: 41476

American (AMR) AF: 0.328 AC: 5004 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3609 AN: 5136

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4822

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10554

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10599 AN: 67988

Other (OTH) AF: 0.201 AC: 423 AN: 2104

Alfa AF: 0.0469 Hom.: 44

Bravo AF: 0.208

Asia WGS AF: 0.455 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.43
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2720382; hg19: chr4-185577470;