rs571470900
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004304.5(ALK):c.4185C>T(p.Thr1395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1395T) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.4185C>T | p.Thr1395= | synonymous_variant | 29/29 | ENST00000389048.8 | |
ALK | NM_001353765.2 | c.981C>T | p.Thr327= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.4185C>T | p.Thr1395= | synonymous_variant | 29/29 | 1 | NM_004304.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250340Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135662
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461842Hom.: 0 Cov.: 36 AF XY: 0.0000289 AC XY: 21AN XY: 727220
GnomAD4 genome AF: 0.000230 AC: 35AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74466
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 27, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 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. - |
Neuroblastoma, susceptibility to, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
ALK-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 02, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at