rs183398286
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000384.3(APOB):āc.2657A>Gā(p.Asn886Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOB | NM_000384.3 | c.2657A>G | p.Asn886Ser | missense_variant | 18/29 | ENST00000233242.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOB | ENST00000233242.5 | c.2657A>G | p.Asn886Ser | missense_variant | 18/29 | 1 | NM_000384.3 | P1 | |
APOB | ENST00000673739.2 | c.*1963A>G | 3_prime_UTR_variant, NMD_transcript_variant | 17/25 | |||||
APOB | ENST00000673882.2 | c.*1963A>G | 3_prime_UTR_variant, NMD_transcript_variant | 17/23 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251374Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135854
GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727248
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74472
ClinVar
Submissions by phenotype
Hypercholesterolemia, autosomal dominant, type B;C4551990:Familial hypobetalipoproteinemia 1 Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jun 15, 2022 | The c.2657A>G p.(Asn886Ser) variant identified in the APOB gene is predicted to result in the substitution of an Asparagine for Serineat amino acid 886/4564 (exon 18/29). This variant is found with low frequency in population databases gnomAD, BRAVO-TOPMed Freeze 8, All of Us (allele frequency=1.1e-4) suggesting it is not a common benign variant in the populations represented in those databases. In silico algorithms do not predict a damaging effect to the function of the canonical protein (REVEL=0.153). This variant reported in ClinVar as a Variant of Uncertain Significance [VarID:237742] and to our current knowledge has not been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity, the c.2657A>Gp.(Asn886Ser) variant identified in the APOB gene is reported as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 25, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.2657A>G (p.N886S) alteration is located in exon 18 (coding exon 18) of the APOB gene. This alteration results from a A to G substitution at nucleotide position 2657, causing the asparagine (N) at amino acid position 886 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at