6-30722392-G-A

Position:

• chr6-30722392-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178014.4(TUBB):​c.58-145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 625,424 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (9 hom., cov: 32)
  • Exomes 𝑓: 0.015 (79 hom.)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.846

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=-0.91).
• BP6: Variant 6-30722392-G-A is Benign according to our data. Variant chr6-30722392-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0151 (7135/473124) while in subpopulation EAS AF= 0.0323 (989/30618). AF 95% confidence interval is 0.0306. There are 79 homozygotes in gnomad4_exome. There are 3714 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1635 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB	NM_178014.4	c.58-145G>A		intron_variant		ENST00000327892.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB	ENST00000327892.13	c.58-145G>A		intron_variant		1	NM_178014.4	P1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1640 AN: 152182 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0151 AC: 7135 AN: 473124 Hom.: 79 Cov.: 5 AF XY: 0.0149 AC XY: 3714 AN XY: 248950

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.0323

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0107 AC: 1635 AN: 152300 Hom.: 9 Cov.: 32 AF XY: 0.0101 AC XY: 752 AN XY: 74486

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00951

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0134 Hom.: 1

Bravo AF: 0.0100

Asia WGS AF: 0.0150 AC: 51 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	-0.91
CADD	Benign	3.1
DANN	Benign	0.76

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: rs148198842; hg19: chr6-30690169;