2-219254033-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001355221.1(TUBA4B):c.12+614G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 592,066 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

TUBA4B
NM_001355221.1 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140

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]

TUBA4B links:

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]

TUBA4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-219254033-G-T is Benign according to our data. Variant chr2-219254033-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1181267.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00515 (783/152180) while in subpopulation AFR AF = 0.0179 (745/41542). AF 95% confidence interval is 0.0169. There are 11 homozygotes in GnomAd4. There are 364 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TUBA4B	NM_001355221.1 link	c.12+614G>T	intron_variant	Intron 1 of 3	ENST00000490341.3	NP_001342150.1
TUBA4A	NM_001278552.2 link	c.-43+62C>A	intron_variant	Intron 1 of 3		NP_001265481.1	P68366-2
TUBA4A	XM_047445674.1 link	c.30+187C>A	intron_variant	Intron 1 of 3		XP_047301630.1
TUBA4A	NM_006000.3 link	c.-175C>A	upstream_gene_variant		ENST00000248437.9	NP_005991.1	P68366-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBA4B	ENST00000490341.3 link	c.12+614G>T		intron_variant	Intron 1 of 3	2	NM_001355221.1	ENSP00000487719.1		Q9H853
TUBA4A	ENST00000248437.9 link	c.-175C>A		upstream_gene_variant		1	NM_006000.3	ENSP00000248437.4		P68366-1

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

780

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00430

GnomAD4 exome

AF:

0.000475

AC:

209

AN:

439886

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

222754

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

AC:

143

AN:

9676

Gnomad4 AMR exome

AF:

0.00157

AC:

AN:

10202

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

11106

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

23676

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

21878

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

38394

Gnomad4 NFE exome

AF:

0.0000333

AC:

AN:

300124

Gnomad4 Remaining exome

AF:

0.00169

AC:

AN:

23082

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00515

AC:

783

AN:

152180

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0179

AC:

0.0179337

AN:

0.0179337

Gnomad4 AMR

AF:

0.00170

AC:

0.00169824

AN:

0.00169824

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000441

AC:

0.0000441488

AN:

0.0000441488

Gnomad4 OTH

AF:

0.00426

AC:

0.00425733

AN:

0.00425733

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000533

Hom.:

Bravo

AF:

0.00568

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 24, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

DANN

Benign

0.73

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over