9-137241340-CCCG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006088.6(TUBB4B):c.-6_-4del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.54

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]

ACMG classification

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 GnomAd at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB4B	NM_006088.6	c.-6_-4del		5_prime_UTR_variant	1/4	ENST00000340384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB4B	ENST00000340384.5	c.-6_-4del		5_prime_UTR_variant	1/4	1	NM_006088.6	P1
TUBB4B	ENST00000604929.1	n.68_70del		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 446 AN: 151838 Hom.: 4 Cov.: 32

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.: 5 AF XY: 0.00359 AC XY: 415 AN XY: 115516

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.: 17 AF XY: 0.00513 AC XY: 3643 AN XY: 710184

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.: 4 Cov.: 32 AF XY: 0.00268 AC XY: 199 AN XY: 74282

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

TUBB4B-related disorder Benign:1

Benign, criteria provided, single submitter

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). -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs370341505; hg19: chr9-140135792;