6-30722324-T-A

Position:

• chr6-30722324-T-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.58-213T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 552,606 control chromosomes in the GnomAD database, including 787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (241 hom., cov: 32)
  • Exomes 𝑓: 0.019 (546 hom.)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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=-0.75).
• BP6: Variant 6-30722324-T-A is Benign according to our data. Variant chr6-30722324-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1181982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB	NM_178014.4	c.58-213T>A		intron_variant		ENST00000327892.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB	ENST00000327892.13	c.58-213T>A		intron_variant		1	NM_178014.4	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3001 AN: 152056 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0187

GnomAD4 exome AF: 0.0188 AC: 7519 AN: 400432 Hom.: 546 Cov.: 3 AF XY: 0.0170 AC XY: 3594 AN XY: 211390

Gnomad4 AFR exome AF: 0.00239

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.00781

Gnomad4 FIN exome AF: 0.0000382

Gnomad4 NFE exome AF: 0.000297

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0198 AC: 3008 AN: 152174 Hom.: 241 Cov.: 32 AF XY: 0.0225 AC XY: 1676 AN XY: 74428

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0107 Hom.: 12

Bravo AF: 0.0293

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.5
DANN	Benign	0.87

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: rs143804865; hg19: chr6-30690101;