rs7693625

Variant names:

• chr4-184651104-A-G
• rs7693625
• NM_152683.4:c.-137-919A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-184651104-A-G
• chr4-184651104-A-T

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-137-919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,986 control chromosomes in the GnomAD database, including 2,326 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 0.16 (2326 hom., cov: 30)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMPOL	NM_152683.4	c.-137-919A>G		intron_variant	Intron 1 of 13	ENST00000314970.11	NP_689896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRIMPOL	ENST00000314970.11	c.-137-919A>G		intron_variant	Intron 1 of 13	1	NM_152683.4	ENSP00000313816.6

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24571 AN: 151868 Hom.: 2326 Cov.: 30

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.162 AC: 24576 AN: 151986 Hom.: 2326 Cov.: 30 AF XY: 0.160 AC XY: 11893 AN XY: 74312

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.179

Alfa AF: 0.0964 Hom.: 150

Bravo AF: 0.162

Asia WGS AF: 0.184 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs7693625; hg19: chr4-185572258;