rs6599418

chr4-2210268-A-Gchr4-2210268-A-T

Variant summary

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

The NM_181808.4(POLN):c.214-1781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,544 control chromosomes in the GnomAD database, including 36,529 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 0.68 (36529 hom., cov: 29)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLN	NM_181808.4	c.214-1781T>C		intron_variant		ENST00000511885.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLN	ENST00000511885.6	c.214-1781T>C		intron_variant		5	NM_181808.4	P1
POLN	ENST00000382865.5	c.214-1781T>C		intron_variant		1		P1
POLN	ENST00000506518.1	n.425-1781T>C		intron_variant, non_coding_transcript_variant		3
POLN	ENST00000515357.5	n.559-1781T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102196 AN: 151426 Hom.: 36468 Cov.: 29

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.675 AC: 102314 AN: 151544 Hom.: 36529 Cov.: 29 AF XY: 0.673 AC XY: 49850 AN XY: 74018

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.663

Alfa AF: 0.576 Hom.: 11567

Bravo AF: 0.694

Asia WGS AF: 0.486 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	6.0
Dann	Benign	0.87

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: rs6599418; hg19: chr4-2211995;