rs529966

Positions:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181808.4(POLN):​c.1731+6066C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,010 control chromosomes in the GnomAD database, including 46,260 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 0.76 ( 46260 hom., cov: 31)

Consequence

POLN
NM_181808.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.336
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POLNNM_181808.4 linkuse as main transcriptc.1731+6066C>T intron_variant ENST00000511885.6 NP_861524.2 Q7Z5Q5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POLNENST00000511885.6 linkuse as main transcriptc.1731+6066C>T intron_variant 5 NM_181808.4 ENSP00000435506.1 Q7Z5Q5-1
ENSG00000290263ENST00000672725.1 linkuse as main transcriptn.*109+19957C>T intron_variant ENSP00000500518.1 A0A5F9ZHQ7

Frequencies

GnomAD3 genomes
AF:
0.761
AC:
115567
AN:
151890
Hom.:
46253
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.506
Gnomad AMI
AF:
0.774
Gnomad AMR
AF:
0.760
Gnomad ASJ
AF:
0.851
Gnomad EAS
AF:
0.625
Gnomad SAS
AF:
0.836
Gnomad FIN
AF:
0.916
Gnomad MID
AF:
0.782
Gnomad NFE
AF:
0.892
Gnomad OTH
AF:
0.756
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.761
AC:
115620
AN:
152010
Hom.:
46260
Cov.:
31
AF XY:
0.763
AC XY:
56665
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.506
Gnomad4 AMR
AF:
0.760
Gnomad4 ASJ
AF:
0.851
Gnomad4 EAS
AF:
0.626
Gnomad4 SAS
AF:
0.836
Gnomad4 FIN
AF:
0.916
Gnomad4 NFE
AF:
0.892
Gnomad4 OTH
AF:
0.754
Alfa
AF:
0.857
Hom.:
25714
Bravo
AF:
0.734
Asia WGS
AF:
0.673
AC:
2337
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
5.6
DANN
Benign
0.78

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs529966; hg19: chr4-2152449; API