rs377214413
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_004304.5(ALK):c.1283-5T>C 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 0.0000198 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004304.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.1283-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000389048.8 | |||
LOC101929386 | XR_007086263.1 | n.447+5958A>G | intron_variant, non_coding_transcript_variant | ||||
LOC101929386 | XR_939920.3 | n.299A>G | non_coding_transcript_exon_variant | 4/10 | |||
ALK | XR_001738688.3 | n.2210-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1283-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004304.5 | P1 | |||
ENST00000655343.1 | n.291+5958A>G | intron_variant, non_coding_transcript_variant | |||||||
ALK | ENST00000618119.4 | c.152-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250968Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135640
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461820Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727200
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 09, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this variant does not alter splicing - |
Neuroblastoma, susceptibility to, 3 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Familial isolated pituitary adenoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Aug 04, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 27, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at