2-219254060-T-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001355221.1(TUBA4B):c.12+641T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 476,568 control chromosomes in the GnomAD database, including 5,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2887 hom., cov: 32)
Exomes 𝑓: 0.11 ( 2676 hom. )
Consequence
TUBA4B
NM_001355221.1 intron
NM_001355221.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.218
Genes affected
TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]
TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 2-219254060-T-G is Benign according to our data. Variant chr2-219254060-T-G is described in ClinVar as [Benign]. Clinvar id is 1260536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TUBA4B | NM_001355221.1 | c.12+641T>G | intron_variant | ENST00000490341.3 | NP_001342150.1 | |||
TUBA4A | NM_001278552.2 | c.-43+35A>C | intron_variant | NP_001265481.1 | ||||
TUBA4A | XM_047445674.1 | c.30+160A>C | intron_variant | XP_047301630.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TUBA4B | ENST00000490341.3 | c.12+641T>G | intron_variant | 2 | NM_001355221.1 | ENSP00000487719 | P1 |
Frequencies
GnomAD3 genomes AF: 0.166 AC: 25173AN: 151950Hom.: 2875 Cov.: 32
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GnomAD4 exome AF: 0.115 AC: 37182AN: 324500Hom.: 2676 Cov.: 4 AF XY: 0.117 AC XY: 19463AN XY: 166992
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GnomAD4 genome AF: 0.166 AC: 25210AN: 152068Hom.: 2887 Cov.: 32 AF XY: 0.163 AC XY: 12150AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2018 | - - |
Computational scores
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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