ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.4954A>C (p.Ile1652Leu)

gnomAD frequency: 0.00003  dbSNP: rs776008744
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001838362 SCV001227528 likely benign Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2024-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002339308 SCV002643931 uncertain significance Cardiovascular phenotype 2021-10-11 criteria provided, single submitter clinical testing The c.4954A>C (p.I1652L) alteration is located in exon 26 (coding exon 26) of the APOB gene. This alteration results from a A to C substitution at nucleotide position 4954, causing the isoleucine (I) at amino acid position 1652 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
New York Genome Center RCV001838362 SCV004046635 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2022-12-19 criteria provided, single submitter clinical testing The c.4954A>C p.(Ile1652Leu) missense variant identified in the APOB gene has previously been deposited in ClinVar as a variant of uncertain significance (2) and likely benign (1) [Variation ID: 857100] and to our current knowledge has not been reported in an affected individual in the literature. The c.4954A>C variant is observed in 10 alleles (~0. 0.002% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMedFreeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.4954A>C variant is located in exon 26 of this 29-exon gene, and predicted to replace a weakly conserved isoleucine amino acid with leucine at position 1652 of the encoded protein. In silico algorithms do not predict a damaging effect to the function of the canonical protein (REVEL=0.038); however, there are no functional studies to support or refute these predictions. Based on available evidence the c.4954A>C p.(Ile1652Leu) variant identified in APOB is classified as a Variant of UncertainSignificance.

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