rs45620539
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001089.3(ABCA3):c.2340C>T(p.His780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,614,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 1 hom. )
Consequence
ABCA3
NM_001089.3 synonymous
NM_001089.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.149
Genes affected
ABCA3 (HGNC:33): (ATP binding cassette subfamily A member 3) The membrane-associated 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 intracellular 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. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 16-2295664-G-A is Benign according to our data. Variant chr16-2295664-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 596957.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1, Likely_benign=2}.
BP7
?
Synonymous conserved (PhyloP=-0.149 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA3 | NM_001089.3 | c.2340C>T | p.His780= | synonymous_variant | 18/33 | ENST00000301732.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA3 | ENST00000301732.10 | c.2340C>T | p.His780= | synonymous_variant | 18/33 | 1 | NM_001089.3 | P1 | |
ABCA3 | ENST00000382381.7 | c.2166C>T | p.His722= | synonymous_variant | 17/32 | 1 | |||
ABCA3 | ENST00000563623.5 | n.2903C>T | non_coding_transcript_exon_variant | 18/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 224AN: 152274Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000490 AC: 123AN: 251178Hom.: 0 AF XY: 0.000368 AC XY: 50AN XY: 135784
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GnomAD4 exome AF: 0.000449 AC: 657AN: 1461684Hom.: 1 Cov.: 32 AF XY: 0.000377 AC XY: 274AN XY: 727150
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GnomAD4 genome ? AF: 0.00147 AC: 224AN: 152392Hom.: 0 Cov.: 32 AF XY: 0.00126 AC XY: 94AN XY: 74524
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Interstitial lung disease due to ABCA3 deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Jan 30, 2019 | This ABCA3 variant (rs45620539) has been identified in large population datasets and the minor allele frequency is neither low enough to consider the variant rare (>0.1%) nor high enough to consider it a population polymorphism (>1%) within the African subpopulation (gnomAD: 115/24972 alleles; 0.46%, no homozygotes). This patient's ethnicity is not reported. A single submitter in ClinVar classifies this variant as uncertain clinical significance (Variation ID: 596957). This variant is reported to be present in one individual with neonatal respiratory distress syndrome (RDS) and absent in an individual without RDS. Bioinformatic analysis predicts that this synonymous variant would not affect normal exon 18 splicing, although this has not been confirmed experimentally to our knowledge. Due to insufficient evidence that this variant is deleterious, the clinical significance of c.2340C>T is uncertain at this time. - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2018 | - - |
Hereditary pulmonary alveolar proteinosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at