rs3136819
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001641.4(APEX1):c.440-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,603,288 control chromosomes in the GnomAD database, including 37 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 0.0091 ( 21 hom., cov: 33)
Exomes 𝑓: 0.00090 ( 16 hom. )
Consequence
APEX1
NM_001641.4 intron
NM_001641.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.06
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0091 (1386/152378) while in subpopulation AFR AF= 0.0317 (1319/41582). AF 95% confidence interval is 0.0303. There are 21 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APEX1 | NM_001641.4 | c.440-61C>T | intron_variant | ENST00000216714.8 | |||
APEX1 | NM_001244249.2 | c.440-61C>T | intron_variant | ||||
APEX1 | NM_080648.3 | c.440-61C>T | intron_variant | ||||
APEX1 | NM_080649.3 | c.440-61C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APEX1 | ENST00000216714.8 | c.440-61C>T | intron_variant | 1 | NM_001641.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00905 AC: 1378AN: 152260Hom.: 21 Cov.: 33
GnomAD3 genomes
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GnomAD4 exome AF: 0.000897 AC: 1302AN: 1450910Hom.: 16 Cov.: 32 AF XY: 0.000791 AC XY: 570AN XY: 721024
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GnomAD4 genome ? AF: 0.00910 AC: 1386AN: 152378Hom.: 21 Cov.: 33 AF XY: 0.00871 AC XY: 649AN XY: 74518
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at