Genetic Variant TUBB4B:c.-6_-4dupGCC (chr9-137241340-C-CCCG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006088.6(TUBB4B):c.-6_-4dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,590,544 control chromosomes in the GnomAD database, including 1,778 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.042 ( 124 hom., cov: 32)

Exomes 𝑓: 0.050 ( 1654 hom. )

Consequence

TUBB4B
NM_006088.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.255

Publications

0 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:

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ACMG classification

Classification was made for transcript

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

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

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.-6_-4dupGCC		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.-6_-4dupGCC	5_prime_UTR	Exon 1 of 4	ENSP00000341289.4	P68371
TUBB4B	ENST00000604929.1	TSL:1	n.68_70dupGCC	non_coding_transcript_exon	Exon 1 of 3
TUBB4B	ENST00000938213.1		c.-6_-4dupGCC	5_prime_UTR	Exon 1 of 4	ENSP00000608272.1

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6430

AN:

151842

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0819

Gnomad EAS

AF:

0.00985

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0506

Gnomad OTH

AF:

0.0466

GnomAD2 exomes

AF:

0.0414

AC:

8563

AN:

206972

AF XY:

0.0417

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0917

Gnomad EAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0531

Gnomad OTH exome

AF:

0.0485

GnomAD4 exome

AF:

0.0497

AC:

71481

AN:

1438588

Hom.:

1654

Cov.:

AF XY:

0.0491

AC XY:

35143

AN XY:

715784

show subpopulations

African (AFR)

AF:

0.0396

AC:

1275

AN:

32222

American (AMR)

AF:

0.0225

AC:

995

AN:

44130

Ashkenazi Jewish (ASJ)

AF:

0.0916

AC:

2362

AN:

25780

East Asian (EAS)

AF:

0.00654

AC:

251

AN:

38360

South Asian (SAS)

AF:

0.0313

AC:

2664

AN:

85182

European-Finnish (FIN)

AF:

0.0288

AC:

1219

AN:

42392

Middle Eastern (MID)

AF:

0.0841

AC:

482

AN:

5734

European-Non Finnish (NFE)

AF:

0.0535

AC:

59099

AN:

1105232

Other (OTH)

AF:

0.0526

AC:

3134

AN:

59556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3383

6766

10148

13531

16914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2248

4496

6744

8992

11240

<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:

0.0424

AC:

6437

AN:

151956

Hom.:

124

Cov.:

AF XY:

0.0409

AC XY:

3041

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0364

AC:

1513

AN:

41510

American (AMR)

AF:

0.0407

AC:

622

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0819

AC:

284

AN:

3466

East Asian (EAS)

AF:

0.00968

AC:

AN:

5164

South Asian (SAS)

AF:

0.0326

AC:

157

AN:

4820

European-Finnish (FIN)

AF:

0.0244

AC:

257

AN:

10536

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0506

AC:

3434

AN:

67882

Other (OTH)

AF:

0.0466

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

311

622

932

1243

1554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0277

Hom.:

Bravo

AF:

0.0422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.26

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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9-137241340-CCCGCCGCCG-CCCGCCGCCGCCG

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