4-184651104-A-G

Variant names:

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

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-137-919A>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
• Publications: 0 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 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.-137-919A>G		intron	N/A	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.-137-919A>G		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-134-919A>G		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.-137-919A>G		intron	N/A	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.-137-919A>G		intron	N/A	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.-285-919A>G		intron	N/A	ENSP00000421913.1	A0A5S6SZ32

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

African (AFR) AF: 0.0613 AC: 2542 AN: 41446

American (AMR) AF: 0.202 AC: 3091 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 619 AN: 3466

East Asian (EAS) AF: 0.162 AC: 838 AN: 5168

South Asian (SAS) AF: 0.184 AC: 885 AN: 4806

European-Finnish (FIN) AF: 0.157 AC: 1652 AN: 10552

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14334 AN: 67962

Other (OTH) AF: 0.179 AC: 378 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.13
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7693625; hg19: chr4-185572258;