Genetic Variant TUBB4B:p.Ile16Ile (chr9-137241408-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP7BS2

The NM_006088.6(TUBB4B):c.48C>T(p.Ile16Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,441,066 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. Synonymous variant affecting the same amino acid position (i.e. I16I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

TUBB4B
NM_006088.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.455

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP7

Synonymous conserved (PhyloP=-0.455 with no splicing effect.

BS2

High AC in GnomAdExome4 at 8 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.48C>T	p.Ile16Ile	synonymous	Exon 1 of 4	NP_006079.1	P68371

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBB4B	ENST00000340384.5	TSL:1 MANE Select	c.48C>T	p.Ile16Ile	synonymous	Exon 1 of 4	ENSP00000341289.4	P68371
TUBB4B	ENST00000604929.1	TSL:1	n.121C>T		non_coding_transcript_exon	Exon 1 of 3
TUBB4B	ENST00000938213.1		c.48C>T	p.Ile16Ile	synonymous	Exon 1 of 4	ENSP00000608272.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000450

AC:

AN:

222368

AF XY:

0.00000809

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1441066

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

717340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31412

American (AMR)

AF:

0.00

AC:

AN:

43588

Ashkenazi Jewish (ASJ)

AF:

0.0000389

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

37056

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000543

AC:

AN:

1104136

Other (OTH)

AF:

0.00

AC:

AN:

59622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.46

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over