6-30720290-C-G

Position:

• chr6-30720290-C-G

Variant summary

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

The ENST00000681435.1(TUBB):​c.-159-2247C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 619,258 control chromosomes in the GnomAD database, including 1,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (934 hom., cov: 32)
  • Exomes 𝑓: 0.033 (498 hom.)
• Consequence: TUBB ENST00000681435.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.322

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=-0.48).
• BP6: Variant 6-30720290-C-G is Benign according to our data. Variant chr6-30720290-C-G is described in ClinVar as [Benign]. Clinvar id is 1233701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB	ENST00000681435.1	c.-159-2247C>G		intron_variant				ENSP00000506665

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12083 AN: 152100 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0918

GnomAD4 exome AF: 0.0334 AC: 15593 AN: 467040 Hom.: 498 Cov.: 4 AF XY: 0.0313 AC XY: 7771 AN XY: 248184

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.0538

Gnomad4 ASJ exome AF: 0.0631

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.00752

Gnomad4 FIN exome AF: 0.0151

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0448

GnomAD4 genome AF: 0.0796 AC: 12110 AN: 152218 Hom.: 934 Cov.: 32 AF XY: 0.0757 AC XY: 5634 AN XY: 74422

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0644

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.0186 Hom.: 24

Bravo AF: 0.0878

Asia WGS AF: 0.0240 AC: 84 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 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Uncertain	0.98

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: rs17189357; hg19: chr6-30688067;