Variant 9-137241340-CCCG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_006088.6(TUBB4B):c.-6_-4delGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,579,322 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 17 hom. )

Consequence

TUBB4B
NM_006088.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.54

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 links:

TUBB4B (HGNC:):

TUBB4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 9-137241340-CCCG-C is Benign according to our data. Variant chr9-137241340-CCCG-C is described in ClinVar as [Benign]. Clinvar id is 3041694.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB4B	NM_006088.6 linkuse as main transcript	c.-6_-4delGCC		5_prime_UTR_variant	1/4	ENST00000340384.5	NP_006079.1	P68371

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB4B	ENST00000340384 linkuse as main transcript	c.-6_-4delGCC		5_prime_UTR_variant	1/4	1	NM_006088.6	ENSP00000341289.4		P68371
TUBB4B	ENST00000604929.1 linkuse as main transcript	n.68_70delGCC		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

446

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00558

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00375

AC:

776

AN:

206972

Hom.:

AF XY:

0.00359

AC XY:

415

AN XY:

115516

show subpopulations

Gnomad AFR exome

AF:

0.00299

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.000655

Gnomad EAS exome

AF:

0.00188

Gnomad SAS exome

AF:

0.00143

Gnomad FIN exome

AF:

0.00340

Gnomad NFE exome

AF:

0.00586

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00531

AC:

7581

AN:

1427370

Hom.:

AF XY:

0.00513

AC XY:

3643

AN XY:

710184

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.000274

Gnomad4 EAS exome

AF:

0.000871

Gnomad4 SAS exome

AF:

0.000820

Gnomad4 FIN exome

AF:

0.00299

Gnomad4 NFE exome

AF:

0.00638

Gnomad4 OTH exome

AF:

0.00375

GnomAD4 genome

AF:

0.00294

AC:

446

AN:

151952

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

199

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000819

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00133

Gnomad4 NFE

AF:

0.00558

Gnomad4 OTH

AF:

0.00143

Bravo

AF:

0.00306

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TUBB4B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

TUBB4B: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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