4-2136314-A-G

Variant names:

• chr4-2136314-A-G
• rs524051
• NM_181808.4:c.1732-5024T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181808.4(POLN):​c.1732-5024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,200 control chromosomes in the GnomAD database, including 45,506 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 0.74 (45506 hom., cov: 33)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLN	NM_181808.4	c.1732-5024T>C		intron_variant	Intron 16 of 25	ENST00000511885.6	NP_861524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.1732-5024T>C		intron_variant	Intron 16 of 25	5	NM_181808.4	ENSP00000435506.1
ENSG00000290263	ENST00000672725.1	n.*110-7058T>C		intron_variant	Intron 13 of 18			ENSP00000500518.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112345 AN: 152082 Hom.: 45492 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.738 AC: 112379 AN: 152200 Hom.: 45506 Cov.: 33 AF XY: 0.742 AC XY: 55236 AN XY: 74424

African (AFR) AF: 0.386 AC: 16013 AN: 41488

American (AMR) AF: 0.747 AC: 11429 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2871 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3513 AN: 5166

South Asian (SAS) AF: 0.824 AC: 3972 AN: 4818

European-Finnish (FIN) AF: 0.972 AC: 10322 AN: 10620

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61628 AN: 68018

Other (OTH) AF: 0.745 AC: 1575 AN: 2114

Alfa AF: 0.836 Hom.: 38761

Bravo AF: 0.704

Asia WGS AF: 0.707 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.72
PhyloP100		-0.10
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: rs524051; hg19: chr4-2138041;