14-20456290-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001641.4(APEX1):​c.246+189T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 152,262 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 550 hom., cov: 33)

Consequence

APEX1
NM_001641.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.907
Variant links:
Genes affected
APEX1 (HGNC:587): (apurinic/apyrimidinic endodeoxyribonuclease 1) The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 14-20456290-T-A is Benign according to our data. Variant chr14-20456290-T-A is described in ClinVar as [Benign]. Clinvar id is 1234224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APEX1NM_001641.4 linkc.246+189T>A intron_variant Intron 3 of 4 ENST00000216714.8 NP_001632.2 P27695Q5TZP7
APEX1NM_001244249.2 linkc.246+189T>A intron_variant Intron 3 of 4 NP_001231178.1 P27695Q5TZP7
APEX1NM_080648.3 linkc.246+189T>A intron_variant Intron 3 of 4 NP_542379.1 P27695Q5TZP7
APEX1NM_080649.3 linkc.246+189T>A intron_variant Intron 3 of 4 NP_542380.1 P27695Q5TZP7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APEX1ENST00000216714.8 linkc.246+189T>A intron_variant Intron 3 of 4 1 NM_001641.4 ENSP00000216714.3 P27695

Frequencies

GnomAD3 genomes
AF:
0.0467
AC:
7112
AN:
152144
Hom.:
547
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.160
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0148
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.0165
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00137
Gnomad OTH
AF:
0.0392
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0468
AC:
7132
AN:
152262
Hom.:
550
Cov.:
33
AF XY:
0.0458
AC XY:
3410
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.160
Gnomad4 AMR
AF:
0.0147
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0164
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00137
Gnomad4 OTH
AF:
0.0388
Alfa
AF:
0.0374
Hom.:
44
Bravo
AF:
0.0531

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 19, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
6.2
DANN
Benign
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs3136818; hg19: chr14-20924449; API