6-30722488-A-T

Position:

• chr6-30722488-A-T

Variant summary

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

The NM_178014.4(TUBB):​c.58-49A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,253,436 control chromosomes in the GnomAD database, including 2,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (670 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1614 hom.)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

Genes affected

TUBB (HGNC:20778): (tubulin beta class I) This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-30722488-A-T is Benign according to our data. Variant chr6-30722488-A-T is described in ClinVar as [Benign]. Clinvar id is 1295941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB	NM_178014.4	c.58-49A>T		intron_variant		ENST00000327892.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB	ENST00000327892.13	c.58-49A>T		intron_variant		1	NM_178014.4	P1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11198 AN: 152150 Hom.: 668 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0731

GnomAD3 exomes AF: 0.0558 AC: 12691 AN: 227276 Hom.: 571 AF XY: 0.0570 AC XY: 7052 AN XY: 123804

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0526

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0358

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0418 AC: 46060 AN: 1101168 Hom.: 1614 Cov.: 14 AF XY: 0.0436 AC XY: 24462 AN XY: 561068

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0368

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0327

Gnomad4 OTH exome AF: 0.0526

GnomAD4 genome AF: 0.0736 AC: 11206 AN: 152268 Hom.: 670 Cov.: 32 AF XY: 0.0731 AC XY: 5445 AN XY: 74470

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0803

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0511 Hom.: 58

Bravo AF: 0.0803

Asia WGS AF: 0.120 AC: 415 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

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs75955575; hg19: chr6-30690265;