6-30722858-G-A

Position:

• chr6-30722858-G-A

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.167-60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,420,080 control chromosomes in the GnomAD database, including 418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (117 hom., cov: 32)
  • Exomes 𝑓: 0.016 (301 hom.)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.57

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=-0.87).
• BP6: Variant 6-30722858-G-A is Benign according to our data. Variant chr6-30722858-G-A is described in ClinVar as [Benign]. Clinvar id is 1226284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB	NM_178014.4	c.167-60G>A		intron_variant		ENST00000327892.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB	ENST00000327892.13	c.167-60G>A		intron_variant		1	NM_178014.4	P1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4694 AN: 152176 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0158 AC: 20052 AN: 1267786 Hom.: 301 Cov.: 17 AF XY: 0.0159 AC XY: 10076 AN XY: 633344

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0380

Gnomad4 EAS exome AF: 0.0119

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.00507

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0202

GnomAD4 genome AF: 0.0308 AC: 4695 AN: 152294 Hom.: 117 Cov.: 32 AF XY: 0.0300 AC XY: 2233 AN XY: 74468

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0227 Hom.: 16

Bravo AF: 0.0350

Asia WGS AF: 0.0140 AC: 48 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

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.048
DANN	Benign	0.64

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: rs17189364; hg19: chr6-30690635;