2-219254060-T-G

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.218
Variant links:
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
TUBA4BNM_001355221.1 linkuse as main transcriptc.12+641T>G intron_variant ENST00000490341.3 NP_001342150.1
TUBA4ANM_001278552.2 linkuse as main transcriptc.-43+35A>C intron_variant NP_001265481.1
TUBA4AXM_047445674.1 linkuse as main transcriptc.30+160A>C intron_variant XP_047301630.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBA4BENST00000490341.3 linkuse as main transcriptc.12+641T>G intron_variant 2 NM_001355221.1 ENSP00000487719 P1

Frequencies

GnomAD3 genomes
AF:
0.166
AC:
25173
AN:
151950
Hom.:
2875
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.322
Gnomad AMI
AF:
0.102
Gnomad AMR
AF:
0.136
Gnomad ASJ
AF:
0.137
Gnomad EAS
AF:
0.154
Gnomad SAS
AF:
0.198
Gnomad FIN
AF:
0.0465
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.0964
Gnomad OTH
AF:
0.179
GnomAD4 exome
AF:
0.115
AC:
37182
AN:
324500
Hom.:
2676
Cov.:
4
AF XY:
0.117
AC XY:
19463
AN XY:
166992
show subpopulations
Gnomad4 AFR exome
AF:
0.320
Gnomad4 AMR exome
AF:
0.126
Gnomad4 ASJ exome
AF:
0.145
Gnomad4 EAS exome
AF:
0.151
Gnomad4 SAS exome
AF:
0.204
Gnomad4 FIN exome
AF:
0.0490
Gnomad4 NFE exome
AF:
0.101
Gnomad4 OTH exome
AF:
0.145
GnomAD4 genome
AF:
0.166
AC:
25210
AN:
152068
Hom.:
2887
Cov.:
32
AF XY:
0.163
AC XY:
12150
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.322
Gnomad4 AMR
AF:
0.135
Gnomad4 ASJ
AF:
0.137
Gnomad4 EAS
AF:
0.154
Gnomad4 SAS
AF:
0.198
Gnomad4 FIN
AF:
0.0465
Gnomad4 NFE
AF:
0.0964
Gnomad4 OTH
AF:
0.178
Alfa
AF:
0.0918
Hom.:
269
Bravo
AF:
0.180
Asia WGS
AF:
0.165
AC:
574
AN:
3478

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
3.4
DANN
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2071385; hg19: chr2-220118782; COSMIC: COSV50281813; COSMIC: COSV50281813; API