chr11-116821001-A-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000482.4(APOA4):c.1057T>G(p.Ser353Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,614,190 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0076 ( 10 hom., cov: 34)
Exomes 𝑓: 0.00088 ( 23 hom. )
Consequence
APOA4
NM_000482.4 missense
NM_000482.4 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 0.601
Genes affected
APOA4 (HGNC:602): (apolipoprotein A4) Apoliprotein (apo) A-IV gene contains 3 exons separated by two introns. A sequence polymorphism has been identified in the 3'UTR of the third exon. The primary translation product is a 396-residue preprotein which after proteolytic processing is secreted its primary site of synthesis, the intestine, in association with chylomicron particles. Although its precise function is not known, apo A-IV is a potent activator of lecithin-cholesterol acyltransferase in vitro. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0064816773).
BP6
?
Variant 11-116821001-A-C is Benign according to our data. Variant chr11-116821001-A-C is described in ClinVar as [Benign]. Clinvar id is 710015.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00758 (1154/152302) while in subpopulation AFR AF= 0.0256 (1062/41550). AF 95% confidence interval is 0.0243. There are 10 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOA4 | NM_000482.4 | c.1057T>G | p.Ser353Ala | missense_variant | 3/3 | ENST00000357780.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOA4 | ENST00000357780.5 | c.1057T>G | p.Ser353Ala | missense_variant | 3/3 | 1 | NM_000482.4 | P1 | |
ENST00000645414.1 | n.169-19A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00759 AC: 1155AN: 152184Hom.: 10 Cov.: 34
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00183 AC: 461AN: 251476Hom.: 10 AF XY: 0.00135 AC XY: 184AN XY: 135916
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GnomAD4 exome AF: 0.000882 AC: 1290AN: 1461888Hom.: 23 Cov.: 87 AF XY: 0.000749 AC XY: 545AN XY: 727244
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GnomAD4 genome ? AF: 0.00758 AC: 1154AN: 152302Hom.: 10 Cov.: 34 AF XY: 0.00737 AC XY: 549AN XY: 74478
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ESP6500AA
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ExAC
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291
Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
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