rs6599418

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-2210268-A-G
• chr4-2210268-A-T

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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

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

African (AFR) AF: 0.914 AC: 37851 AN: 41418

American (AMR) AF: 0.690 AC: 10503 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1991 AN: 3458

East Asian (EAS) AF: 0.382 AC: 1959 AN: 5134

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4812

European-Finnish (FIN) AF: 0.623 AC: 6443 AN: 10334

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39073 AN: 67850

Other (OTH) AF: 0.663 AC: 1394 AN: 2102

Alfa AF: 0.576 Hom.: 12854

Bravo AF: 0.694

Asia WGS AF: 0.486 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.0
DANN	Benign	0.87
PhyloP100		-0.85
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: rs6599418; hg19: chr4-2211995;