chr6-30720290-C-G

Variant names:

• chr6-30720290-C-G
• rs17189357
• ENST00000681435.1:c.-159-2247C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.48).
• BP6: Variant 6-30720290-C-G is Benign according to our data. Variant chr6-30720290-C-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681435.1. 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.-217C>G		upstream_gene	N/A	NP_821133.1	Q5SU16
	TUBB	NM_001293214.2		c.-217C>G		upstream_gene	N/A	NP_001280143.1
	TUBB	NM_001293213.2		c.-217C>G		upstream_gene	N/A	NP_001280142.1	B4DMJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB	ENST00000681435.1		c.-159-2247C>G		intron	N/A	ENSP00000506665.1	Q5ST81
	TUBB	ENST00000327892.13	TSL:1 MANE Select	c.-217C>G		upstream_gene	N/A	ENSP00000339001.7	P07437
	TUBB	ENST00000940307.1		c.-217C>G		upstream_gene	N/A	ENSP00000610366.1

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

African (AFR) AF: 0.201 AC: 2509 AN: 12500

American (AMR) AF: 0.0538 AC: 1068 AN: 19838

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 886 AN: 14032

East Asian (EAS) AF: 0.00129 AC: 40 AN: 31102

South Asian (SAS) AF: 0.00752 AC: 354 AN: 47082

European-Finnish (FIN) AF: 0.0151 AC: 555 AN: 36874

Middle Eastern (MID) AF: 0.0535 AC: 107 AN: 2000

European-Non Finnish (NFE) AF: 0.0321 AC: 8885 AN: 277056

Other (OTH) AF: 0.0448 AC: 1189 AN: 26556

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

African (AFR) AF: 0.199 AC: 8264 AN: 41506

American (AMR) AF: 0.0644 AC: 985 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 217 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4824

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2218 AN: 68010

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0186 Hom.: 24

Bravo AF: 0.0878

Asia WGS AF: 0.0240 AC: 84 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	-0.48
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		0.32
PromoterAI		0.033	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17189357; hg19: chr6-30688067;