6-30720798-G-C

Position:

• chr6-30720798-G-C

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.57+235G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,330 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (579 hom., cov: 33)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.317

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=-0.67).
• BP6: Variant 6-30720798-G-C is Benign according to our data. Variant chr6-30720798-G-C is described in ClinVar as [Benign]. Clinvar id is 1246819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB	NM_178014.4	c.57+235G>C		intron_variant		ENST00000327892.13
TUBB	NM_001293213.2	c.57+235G>C		intron_variant
TUBB	NM_001293214.2	c.34+258G>C		intron_variant
TUBB	NR_120608.2	n.212+235G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB	ENST00000327892.13	c.57+235G>C		intron_variant		1	NM_178014.4	P1
TUBB	ENST00000681435.1	c.-159-1739G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11057 AN: 152212 Hom.: 579 Cov.: 33

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0521

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0726 AC: 11058 AN: 152330 Hom.: 579 Cov.: 33 AF XY: 0.0665 AC XY: 4954 AN XY: 74492

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0685

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0978 Hom.: 118

Bravo AF: 0.0693

Asia WGS AF: 0.00433 AC: 16 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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.1
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3132583; hg19: chr6-30688575;