4-2210268-A-T

Variant names:

• chr4-2210268-A-T
• rs6599418
• NM_181808.4:c.214-1781T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181808.4(POLN):​c.214-1781T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

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.214-1781T>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.214-1781T>A		intron	N/A	ENSP00000435506.1	Q7Z5Q5-1
	POLN	ENST00000382865.5	TSL:1	c.214-1781T>A		intron	N/A	ENSP00000372316.1	Q7Z5Q5-1
	ENSG00000290263	ENST00000672725.1		n.1804-1781T>A		intron	N/A	ENSP00000500518.1	A0A5F9ZHQ7

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 12854

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.6
DANN	Benign	0.85
PhyloP100		-0.85

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: rs6599418; hg19: chr4-2211995;