9-137241340-C-CCCGCCG

Variant summary

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

The NM_006088.6(TUBB4B):c.-9_-4dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,590,806 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (6 hom.)
• Consequence: TUBB4B NM_006088.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.255

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-C-CCCGCCG is Benign according to our data. Variant chr9-137241340-C-CCCGCCG is described in ClinVar as [Likely_benign]. Clinvar id is 3045573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB4B	NM_006088.6	c.-9_-4dup		5_prime_UTR_variant	1/4	ENST00000340384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB4B	ENST00000340384.5	c.-9_-4dup		5_prime_UTR_variant	1/4	1	NM_006088.6	P1
TUBB4B	ENST00000604929.1	n.65_70dup		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 93 AN: 151852 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000773 AC: 160 AN: 206972 Hom.: 0 AF XY: 0.000762 AC XY: 88 AN XY: 115516

Gnomad AFR exome AF: 0.000362

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.000764

Gnomad EAS exome AF: 0.000940

Gnomad SAS exome AF: 0.00107

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.000487

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000738 AC: 1062 AN: 1438840 Hom.: 6 Cov.: 31 AF XY: 0.000771 AC XY: 552 AN XY: 715920

Gnomad4 AFR exome AF: 0.000403

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.000969

Gnomad4 EAS exome AF: 0.00266

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.000595

Gnomad4 OTH exome AF: 0.000722

GnomAD4 genome AF: 0.000612 AC: 93 AN: 151966 Hom.: 0 Cov.: 32 AF XY: 0.000646 AC XY: 48 AN XY: 74292

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.000619

Gnomad4 OTH AF: 0.000476

Bravo AF: 0.000555

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TUBB4B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 08, 2024

This variant is classified as likely 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

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;