4-2139015-A-G

Variant names:

• chr4-2139015-A-G
• rs482519
• NM_181808.4:c.1732-7725T>C

Variant summary

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

The ENST00000672725.1(ENSG00000290263):​n.*110-9759T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 151,872 control chromosomes in the GnomAD database, including 58,319 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 0.87 (58319 hom., cov: 30)
• Consequence: ENSG00000290263 ENST00000672725.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 5 publications found

Genes affected

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

ENSG00000290263 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672725.1. 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
	POLN	NM_181808.4	MANE Select	c.1732-7725T>C		intron	N/A	NP_861524.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLN	ENST00000511885.6	TSL:5 MANE Select	c.1732-7725T>C		intron	N/A	ENSP00000435506.1
	POLN	ENST00000382865.5	TSL:1	c.1732-7725T>C		intron	N/A	ENSP00000372316.1
	POLN	ENST00000511098.1	TSL:1	c.628-7725T>C		intron	N/A	ENSP00000426401.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132366 AN: 151756 Hom.: 58281 Cov.: 30

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.872 AC: 132464 AN: 151872 Hom.: 58319 Cov.: 30 AF XY: 0.871 AC XY: 64637 AN XY: 74238

African (AFR) AF: 0.778 AC: 32182 AN: 41378

American (AMR) AF: 0.833 AC: 12739 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3366 AN: 5168

South Asian (SAS) AF: 0.875 AC: 4197 AN: 4798

European-Finnish (FIN) AF: 0.974 AC: 10270 AN: 10540

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63696 AN: 67910

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.907 Hom.: 70455

Bravo AF: 0.853

Asia WGS AF: 0.741 AC: 2576 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	0.38
DANN	Benign	0.25
PhyloP100		-2.2
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: rs482519; hg19: chr4-2140742;