4-184654487-G-C

Variant names:

• chr4-184654487-G-C
• rs2705883
• NM_152683.4:c.-60+2387G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152683.4(PRIMPOL):​c.-60+2387G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 20)
  • Failed GnomAD Quality Control
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	NM_152683.4	MANE Select	c.-60+2387G>C		intron	N/A	NP_689896.1
	PRIMPOL	NM_001345891.2		c.-60+2387G>C		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-57+2387G>C		intron	N/A	NP_001332821.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.-60+2387G>C		intron	N/A	ENSP00000313816.6
	PRIMPOL	ENST00000512834.5	TSL:1	c.-60+2387G>C		intron	N/A	ENSP00000425316.1
	PRIMPOL	ENST00000515774.5	TSL:1	c.-208+2387G>C		intron	N/A	ENSP00000421913.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 118254 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 118254 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 56102

African (AFR) AF: 0.00 AC: 0 AN: 34312

American (AMR) AF: 0.00 AC: 0 AN: 11704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2854

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 3530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53228

Other (OTH) AF: 0.00 AC: 0 AN: 1600

Alfa AF: 0.00 Hom.: 958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.37
PhyloP100		-0.29

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: rs2705883; hg19: chr4-185575641;