4-184651571-G-A

Variant names:

• chr4-184651571-G-A
• rs2705881
• NM_152683.4:c.-137-452G>A

Variant summary

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

The NM_152683.4(PRIMPOL):​c.-137-452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,152 control chromosomes in the GnomAD database, including 3,867 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 (3867 hom., cov: 32)
• Consequence: PRIMPOL NM_152683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.683 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.-137-452G>A		intron	N/A	NP_689896.1	Q96LW4-1
	PRIMPOL	NM_001345891.2		c.-137-452G>A		intron	N/A	NP_001332820.1
	PRIMPOL	NM_001345892.2		c.-134-452G>A		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.-137-452G>A		intron	N/A	ENSP00000313816.6	Q96LW4-1
	PRIMPOL	ENST00000512834.5	TSL:1	c.-137-452G>A		intron	N/A	ENSP00000425316.1	Q96LW4-2
	PRIMPOL	ENST00000515774.5	TSL:1	c.-285-452G>A		intron	N/A	ENSP00000421913.1	A0A5S6SZ32

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28981 AN: 152032 Hom.: 3866 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.191 AC: 28992 AN: 152152 Hom.: 3867 Cov.: 32 AF XY: 0.199 AC XY: 14769 AN XY: 74376

African (AFR) AF: 0.120 AC: 5002 AN: 41514

American (AMR) AF: 0.329 AC: 5031 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3466

East Asian (EAS) AF: 0.702 AC: 3632 AN: 5176

South Asian (SAS) AF: 0.314 AC: 1514 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10570

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10983 AN: 68014

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.0915 Hom.: 122

Bravo AF: 0.203

Asia WGS AF: 0.461 AC: 1599 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	3.2
DANN	Benign	0.45
PhyloP100		0.010
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: rs2705881; hg19: chr4-185572725;