6-30720650-G-T

Variant names:

• chr6-30720650-G-T
• rs3132584
• NM_178014.4:c.57+87G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_178014.4(TUBB):​c.57+87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,155,722 control chromosomes in the GnomAD database, including 29,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6353 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22705 hom.)
• Consequence: TUBB NM_178014.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.782
• Publications: 42 publications found

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]

TUBB Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations 6

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multiple benign circumferential skin creases on limbs 1

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P
• TUBB3-related tubulinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• multiple benign circumferential skin creases on limbs

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-30720650-G-T is Benign according to our data. Variant chr6-30720650-G-T is described in ClinVar as Benign. ClinVar VariationId is 1240826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178014.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB	NM_178014.4	MANE Select	c.57+87G>T		intron	N/A	NP_821133.1	Q5SU16
	TUBB	NM_001293214.2		c.34+110G>T		intron	N/A	NP_001280143.1
	TUBB	NM_001293213.2		c.57+87G>T		intron	N/A	NP_001280142.1	B4DMJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB	ENST00000327892.13	TSL:1 MANE Select	c.57+87G>T		intron	N/A	ENSP00000339001.7	P07437
	TUBB	ENST00000940307.1		c.57+87G>T		intron	N/A	ENSP00000610366.1
	TUBB	ENST00000940306.1		c.57+87G>T		intron	N/A	ENSP00000610365.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39506 AN: 151938 Hom.: 6331 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.200 AC: 200257 AN: 1003666 Hom.: 22705 AF XY: 0.197 AC XY: 101113 AN XY: 512236

African (AFR) AF: 0.461 AC: 10313 AN: 22392

American (AMR) AF: 0.146 AC: 4694 AN: 32248

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 3866 AN: 19928

East Asian (EAS) AF: 0.193 AC: 7006 AN: 36224

South Asian (SAS) AF: 0.144 AC: 9784 AN: 68142

European-Finnish (FIN) AF: 0.109 AC: 5496 AN: 50320

Middle Eastern (MID) AF: 0.224 AC: 1055 AN: 4704

European-Non Finnish (NFE) AF: 0.205 AC: 148577 AN: 725146

Other (OTH) AF: 0.212 AC: 9466 AN: 44562

GnomAD4 genome AF: 0.260 AC: 39560 AN: 152056 Hom.: 6353 Cov.: 32 AF XY: 0.250 AC XY: 18610 AN XY: 74342

African (AFR) AF: 0.453 AC: 18760 AN: 41410

American (AMR) AF: 0.187 AC: 2861 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3468

East Asian (EAS) AF: 0.177 AC: 917 AN: 5182

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10590

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13738 AN: 67984

Other (OTH) AF: 0.268 AC: 565 AN: 2112

Alfa AF: 0.227 Hom.: 14448

Bravo AF: 0.276

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.24
PhyloP100		-0.78
PromoterAI		0.0079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3132584; hg19: chr6-30688427; COSMIC: COSV58357732; COSMIC: COSV58357732;