chr1-161223055-CCACACACACACA-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_001643.2(APOA2):c.53-17_53-6delTGTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,423,886 control chromosomes in the GnomAD database, including 2,403 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_001643.2 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOA2 | ENST00000367990.7 | c.53-17_53-6delTGTGTGTGTGTG | splice_region_variant, intron_variant | Intron 2 of 3 | 1 | NM_001643.2 | ENSP00000356969.3 | |||
APOA2 | ENST00000470459.6 | c.53-17_53-6delTGTGTGTGTGTG | splice_region_variant, intron_variant | Intron 2 of 4 | 5 | ENSP00000477031.1 |
Frequencies
GnomAD3 genomes AF: 0.151 AC: 22251AN: 147474Hom.: 1803 Cov.: 0
GnomAD3 exomes AF: 0.177 AC: 34517AN: 195520Hom.: 491 AF XY: 0.172 AC XY: 18299AN XY: 106664
GnomAD4 exome AF: 0.149 AC: 211500AN: 1423886Hom.: 2403 AF XY: 0.147 AC XY: 104475AN XY: 708466
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.151 AC: 22243AN: 147584Hom.: 1802 Cov.: 0 AF XY: 0.151 AC XY: 10801AN XY: 71700
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: APOA2 c.53-17_53-6delTGTGTGTGTGTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.18 in 195520 control chromosomes, predominantly at a frequency of 0.27 within the East Asian subpopulation in the gnomAD database, including 85 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 13500-folds over the estimated maximal expected allele frequency for a pathogenic variant in APOA2 causing Early Onset Coronary Artery Disease phenotype (2e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.53-17_53-6delTGTGTGTGTGTG in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at