chr6-30720798-G-C

Variant names:

• chr6-30720798-G-C
• rs3132583
• NM_178014.4:c.57+235G>C

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+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
• Publications: 7 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=-0.67).
• BP6: Variant 6-30720798-G-C is Benign according to our data. Variant chr6-30720798-G-C is described in ClinVar as Benign. ClinVar VariationId 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.

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+235G>C		intron	N/A	NP_821133.1	Q5SU16
	TUBB	NM_001293214.2		c.34+258G>C		intron	N/A	NP_001280143.1
	TUBB	NM_001293213.2		c.57+235G>C		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+235G>C		intron	N/A	ENSP00000339001.7	P07437
	TUBB	ENST00000940307.1		c.57+235G>C		intron	N/A	ENSP00000610366.1
	TUBB	ENST00000940306.1		c.57+235G>C		intron	N/A	ENSP00000610365.1

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

African (AFR) AF: 0.0388 AC: 1611 AN: 41574

American (AMR) AF: 0.0332 AC: 508 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.0685 AC: 727 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7844 AN: 68030

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0978 Hom.: 118

Bravo AF: 0.0693

Asia WGS AF: 0.00433 AC: 16 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	-0.67
CADD	Benign	5.1
DANN	Benign	0.92
PhyloP100		0.32
PromoterAI		-0.071	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3132583; hg19: chr6-30688575;