chr4-2101369-C-T

Variant names:

• chr4-2101369-C-T
• rs1923775
• NM_181808.4:c.1983-5436G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLN	NM_181808.4	MANE Select	c.1983-5436G>A		intron	N/A	NP_861524.2	Q7Z5Q5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLN	ENST00000511885.6	TSL:5 MANE Select	c.1983-5436G>A		intron	N/A	ENSP00000435506.1	Q7Z5Q5-1
	POLN	ENST00000382865.5	TSL:1	c.1983-5436G>A		intron	N/A	ENSP00000372316.1	Q7Z5Q5-1
	POLN	ENST00000511098.1	TSL:1	c.879-5436G>A		intron	N/A	ENSP00000426401.1	H0YA88

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

African (AFR) AF: 0.239 AC: 9930 AN: 41474

American (AMR) AF: 0.701 AC: 10712 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3761 AN: 5176

South Asian (SAS) AF: 0.685 AC: 3300 AN: 4820

European-Finnish (FIN) AF: 0.768 AC: 8125 AN: 10586

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49563 AN: 67962

Other (OTH) AF: 0.610 AC: 1288 AN: 2110

Alfa AF: 0.684 Hom.: 153237

Bravo AF: 0.566

Asia WGS AF: 0.646 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.66
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: rs1923775; hg19: chr4-2103096;