dbSNP rs2307490: APEX1:c.-82A>G (chr14-20455381-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001641.4(APEX1):c.-82A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 567,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

APEX1
NM_001641.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.594

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

APEX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS2

High AC in GnomAd4 at 151 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APEX1	NM_001641.4	MANE Select	c.-82A>G	5_prime_UTR	Exon 1 of 5	NP_001632.2
APEX1	NM_001244249.2		c.-77A>G	5_prime_UTR	Exon 1 of 5	NP_001231178.1	Q5TZP7
APEX1	NM_080648.3		c.-69+53A>G	intron	N/A	NP_542379.1	Q5TZP7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APEX1	ENST00000216714.8	TSL:1 MANE Select	c.-82A>G	5_prime_UTR	Exon 1 of 5	ENSP00000216714.3	P27695
APEX1	ENST00000398030.8	TSL:1	c.-69+53A>G	intron	N/A	ENSP00000381111.4	P27695
APEX1	ENST00000555414.5	TSL:1	c.-69+43A>G	intron	N/A	ENSP00000451979.1	P27695

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00116

AC:

482

AN:

415482

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

215

AN XY:

219220

show subpopulations

African (AFR)

AF:

0.000170

AC:

AN:

11732

American (AMR)

AF:

0.0000582

AC:

AN:

17184

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

12490

East Asian (EAS)

AF:

0.00

AC:

AN:

27024

South Asian (SAS)

AF:

0.00

AC:

AN:

44936

European-Finnish (FIN)

AF:

0.00307

AC:

AN:

25720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1768

European-Non Finnish (NFE)

AF:

0.00142

AC:

357

AN:

250954

Other (OTH)

AF:

0.00106

AC:

AN:

23674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000992

AC:

151

AN:

152262

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41554

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00165

AC:

112

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.000691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.8

(source)

DANN

Benign

0.64

PhyloP100

-0.59

PromoterAI

-0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over