2-29531941-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004304.5(ALK):c.1128C>T(p.Leu376Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,614,182 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004304.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.1128C>T | p.Leu376Leu | synonymous_variant | Exon 4 of 29 | 1 | NM_004304.5 | ENSP00000373700.3 | ||
ALK | ENST00000618119.4 | c.-4C>T | 5_prime_UTR_variant | Exon 3 of 28 | 5 | ENSP00000482733.1 |
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152218Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00148 AC: 372AN: 251250Hom.: 5 AF XY: 0.00198 AC XY: 269AN XY: 135784
GnomAD4 exome AF: 0.000629 AC: 919AN: 1461846Hom.: 10 Cov.: 32 AF XY: 0.000919 AC XY: 668AN XY: 727222
GnomAD4 genome AF: 0.000394 AC: 60AN: 152336Hom.: 1 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74484
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Benign:2
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not provided Benign:1
See Variant Classification Assertion Criteria. -
Hereditary cancer-predisposing syndrome Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at