Genetic Variant TUBB4B:c.-29C>G (chr9-137241332-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006088.6(TUBB4B):c.-29C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,591,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

TUBB4B
NM_006088.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Publications

6 publications found

Variant links:

Genes affected

TUBB4B (HGNC:20771): (tubulin beta 4B class IVb) Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. Implicated in Leber congenital amaurosis with early-onset deafness. [provided by Alliance of Genome Resources, Apr 2022]

TUBB4B Gene-Disease associations (from GenCC):

TUBB4B-related ciliopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Leber congenital amaurosis with early-onset deafness
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

TUBB4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006088.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB4B	NM_006088.6	MANE Select	c.-29C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_006079.1	P68371
	TUBB4B	NM_006088.6	MANE Select	c.-29C>G		5_prime_UTR	Exon 1 of 4	NP_006079.1	P68371

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUBB4B	ENST00000340384.5	TSL:1 MANE Select	c.-29C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000341289.4	P68371
TUBB4B	ENST00000340384.5	TSL:1 MANE Select	c.-29C>G	5_prime_UTR	Exon 1 of 4	ENSP00000341289.4	P68371
TUBB4B	ENST00000604929.1	TSL:1	n.45C>G	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000398

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000148

AC:

AN:

216792

AF XY:

0.000174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000400

AC:

576

AN:

1439966

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

291

AN XY:

716462

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32426

American (AMR)

AF:

0.000113

AC:

AN:

44098

Ashkenazi Jewish (ASJ)

AF:

0.000116

AC:

AN:

25876

East Asian (EAS)

AF:

0.00

AC:

AN:

38540

South Asian (SAS)

AF:

0.0000352

AC:

AN:

85338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.000500

AC:

553

AN:

1106954

Other (OTH)

AF:

0.000184

AC:

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000244

AC:

AN:

151906

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41434

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000398

AC:

AN:

67856

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.3

(source)

DANN

Benign

0.23

PhyloP100

0.24

PromoterAI

0.065

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over