rs618262

Positions:

• chr4-2163214-C-A
• chr4-2163214-C-T

Variant summary

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

The NM_181808.4(POLN):​c.1555-4003G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,126 control chromosomes in the GnomAD database, including 55,184 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 0.84 (55184 hom., cov: 31)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLN	NM_181808.4	c.1555-4003G>T		intron_variant		ENST00000511885.6	NP_861524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.1555-4003G>T		intron_variant		5	NM_181808.4	ENSP00000435506	P1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128101 AN: 152006 Hom.: 55154 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.843 AC: 128182 AN: 152126 Hom.: 55184 Cov.: 31 AF XY: 0.843 AC XY: 62716 AN XY: 74378

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.819

Alfa AF: 0.921 Hom.: 30452

Bravo AF: 0.820

Asia WGS AF: 0.730 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.69

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: rs618262; hg19: chr4-2164941;