rs45502600
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001089.3(ABCA3):c.2514-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,548,062 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001089.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA3 | NM_001089.3 | c.2514-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000301732.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA3 | ENST00000301732.10 | c.2514-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001089.3 | P1 | |||
ABCA3 | ENST00000382381.7 | c.2340-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
ABCA3 | ENST00000563623.5 | n.3077-8C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0224 AC: 3403AN: 152218Hom.: 130 Cov.: 33
GnomAD3 exomes AF: 0.00613 AC: 938AN: 152910Hom.: 31 AF XY: 0.00483 AC XY: 391AN XY: 81020
GnomAD4 exome AF: 0.00273 AC: 3808AN: 1395726Hom.: 128 Cov.: 36 AF XY: 0.00246 AC XY: 1694AN XY: 688558
GnomAD4 genome ? AF: 0.0224 AC: 3411AN: 152336Hom.: 131 Cov.: 33 AF XY: 0.0217 AC XY: 1620AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 2514-8C>T in intron 19 of ABCA3: This variant is not expected to have clinical s ignificance because it has been identified in 6.5% (280/4282) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs45502600). - |
Interstitial lung disease due to ABCA3 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at