4-184651670-C-T

Variant names:

• chr4-184651670-C-T
• rs7699420
• NM_152683.4:c.-137-353C>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.-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
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	NM_152683.4	MANE Select	c.-137-353C>T		intron	N/A	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.-137-353C>T		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-134-353C>T		intron	N/A	NP_001332821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMPOL	ENST00000314970.11	TSL:1 MANE Select	c.-137-353C>T		intron	N/A	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.-137-353C>T		intron	N/A	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.-285-353C>T		intron	N/A	ENSP00000421913.1	A0A5S6SZ32

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

African (AFR) AF: 0.740 AC: 30653 AN: 41426

American (AMR) AF: 0.657 AC: 10032 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2873 AN: 3466

East Asian (EAS) AF: 0.299 AC: 1539 AN: 5148

South Asian (SAS) AF: 0.684 AC: 3296 AN: 4816

European-Finnish (FIN) AF: 0.847 AC: 8946 AN: 10562

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56909 AN: 67922

Other (OTH) AF: 0.765 AC: 1619 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		0.069
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: rs7699420; hg19: chr4-185572824;