9-137241332-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006088.6(TUBB4B):c.-29C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,591,822 control chromosomes in the GnomAD database, including 2,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (1463 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1434 hom.)
• Consequence: TUBB4B NM_006088.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.245

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 9-137241332-C-A is Benign according to our data. Variant chr9-137241332-C-A is described in ClinVar as [Benign]. Clinvar id is 1182505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB4B	NM_006088.6	c.-29C>A		5_prime_UTR_variant	1/4	ENST00000340384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB4B	ENST00000340384.5	c.-29C>A		5_prime_UTR_variant	1/4	1	NM_006088.6	P1
TUBB4B	ENST00000604929.1	n.45C>A		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12333 AN: 151782 Hom.: 1457 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0142

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.0647

GnomAD3 exomes AF: 0.0288 AC: 6247 AN: 216792 Hom.: 489 AF XY: 0.0244 AC XY: 2949 AN XY: 120802

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0397

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.0330

Gnomad SAS exome AF: 0.0195

Gnomad FIN exome AF: 0.000473

Gnomad NFE exome AF: 0.00297

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0128 AC: 18423 AN: 1439924 Hom.: 1434 Cov.: 31 AF XY: 0.0122 AC XY: 8747 AN XY: 716436

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.0423

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.0383

Gnomad4 SAS exome AF: 0.0200

Gnomad4 FIN exome AF: 0.000485

Gnomad4 NFE exome AF: 0.00210

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.0815 AC: 12380 AN: 151898 Hom.: 1463 Cov.: 33 AF XY: 0.0788 AC XY: 5856 AN XY: 74292

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.0142

Gnomad4 EAS AF: 0.0407

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00299

Gnomad4 OTH AF: 0.0692

Alfa AF: 0.00780 Hom.: 20

Bravo AF: 0.0927

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.8
Dann	Benign	0.41
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

LitVar

Other links and lift over

dbSNP: rs11545612; hg19: chr9-140135784;