4-2139015-A-G

Position:

• chr4-2139015-A-G

Variant summary

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

The NM_181808.4(POLN):​c.1732-7725T>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: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLN	NM_181808.4	c.1732-7725T>C		intron_variant		ENST00000511885.6	NP_861524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.1732-7725T>C		intron_variant		5	NM_181808.4	ENSP00000435506.1
ENSG00000290263	ENST00000672725.1	n.*110-9759T>C		intron_variant				ENSP00000500518.1

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

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.974

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.839

Alfa AF: 0.919 Hom.: 48992

Bravo AF: 0.853

Asia WGS AF: 0.741 AC: 2576 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	0.38
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs482519; hg19: chr4-2140742;