19-1041940-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_019112.4(ABCA7):c.273del(p.Arg93AlafsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 1,590,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
ABCA7
NM_019112.4 frameshift
NM_019112.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.53
Genes affected
ABCA7 (HGNC:37): (ATP binding cassette subfamily A member 7) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This full transporter has been detected predominantly in myelo-lymphatic tissues with the highest expression in peripheral leukocytes, thymus, spleen, and bone marrow. The function of this protein is not yet known; however, the expression pattern suggests a role in lipid homeostasis in cells of the immune system. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-1041940-GC-G is Pathogenic according to our data. Variant chr19-1041940-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1678180.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA7 | NM_019112.4 | c.273del | p.Arg93AlafsTer2 | frameshift_variant | 4/47 | ENST00000263094.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA7 | ENST00000263094.11 | c.273del | p.Arg93AlafsTer2 | frameshift_variant | 4/47 | 5 | NM_019112.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000134 AC: 3AN: 223470Hom.: 0 AF XY: 0.00000808 AC XY: 1AN XY: 123836
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GnomAD4 exome AF: 0.0000271 AC: 39AN: 1438366Hom.: 0 Cov.: 32 AF XY: 0.0000210 AC XY: 15AN XY: 715470
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Mar 24, 2022 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at