9-137241299-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006088.6(TUBB4B):c.-62G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,557,010 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (186 hom.)
• Consequence: TUBB4B NM_006088.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-137241299-G-T is Benign according to our data. Variant chr9-137241299-G-T is described in ClinVar as [Benign]. Clinvar id is 1245035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1536 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB4B	NM_006088.6	c.-62G>T		5_prime_UTR_variant	1/4	ENST00000340384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB4B	ENST00000340384.5	c.-62G>T		5_prime_UTR_variant	1/4	1	NM_006088.6	P1
TUBB4B	ENST00000604929.1	n.12G>T		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1536 AN: 152040 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.00534 AC: 7495 AN: 1404852 Hom.: 186 Cov.: 29 AF XY: 0.00518 AC XY: 3618 AN XY: 697844

Gnomad4 AFR exome AF: 0.000514

Gnomad4 AMR exome AF: 0.000123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000181

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.00312

Gnomad4 OTH exome AF: 0.00555

GnomAD4 genome AF: 0.0101 AC: 1535 AN: 152158 Hom.: 63 Cov.: 33 AF XY: 0.0143 AC XY: 1065 AN XY: 74388

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.00449

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00716 Hom.: 1

Bravo AF: 0.00157

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.86

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: rs185668265; hg19: chr9-140135751; COSMIC: COSV100458274; COSMIC: COSV100458274;