chr4-2101369-C-T

Position:

• chr4-2101369-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.1983-5436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,092 control chromosomes in the GnomAD database, including 30,232 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 0.59 (30232 hom., cov: 33)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLN	NM_181808.4	c.1983-5436G>A		intron_variant		ENST00000511885.6	NP_861524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.1983-5436G>A		intron_variant		5	NM_181808.4	ENSP00000435506.1
ENSG00000290263	ENST00000672725.1	n.*303-5436G>A		intron_variant				ENSP00000500518.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89768 AN: 151972 Hom.: 30214 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.590 AC: 89798 AN: 152092 Hom.: 30232 Cov.: 33 AF XY: 0.597 AC XY: 44377 AN XY: 74378

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.610

Alfa AF: 0.702 Hom.: 75323

Bravo AF: 0.566

Asia WGS AF: 0.646 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Benign	0.74

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: rs1923775; hg19: chr4-2103096;