Variant chr14-20457510-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001641.4(APEX1):c.*2A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,578 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 27 hom. )

Consequence

APEX1
NM_001641.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

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]

APEX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-20457510-A-T is Benign according to our data. Variant chr14-20457510-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644051.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
APEX1	NM_001641.4 linkuse as main transcript	c.*2A>T	3_prime_UTR_variant	5/5	ENST00000216714.8
APEX1	NM_001244249.2 linkuse as main transcript	c.*2A>T	3_prime_UTR_variant	5/5
APEX1	NM_080648.3 linkuse as main transcript	c.*2A>T	3_prime_UTR_variant	5/5
APEX1	NM_080649.3 linkuse as main transcript	c.*2A>T	3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APEX1	ENST00000216714.8 linkuse as main transcript	c.*2A>T		3_prime_UTR_variant	5/5	1	NM_001641.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00601

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00336

AC:

844

AN:

250868

Hom.:

AF XY:

0.00365

AC XY:

495

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.00532

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00487

AC:

7111

AN:

1461340

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

3623

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00543

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00325

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00556

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00342

AC:

520

AN:

152238

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00601

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00538

Hom.:

Bravo

AF:

0.00316

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

APEX1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over