rs9295910

Variant names:

• chr6-30719937-T-A
• rs9295910
• ENST00000681435.1:c.-160+2298T>A

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.-160+2298T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 151,964 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1184 hom., cov: 32)
• Consequence: TUBB ENST00000681435.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.485
• Publications: 5 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=-0.81).
• BP6: Variant 6-30719937-T-A is Benign according to our data. Variant chr6-30719937-T-A is described in ClinVar as Benign. ClinVar VariationId is 1289698.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB	ENST00000681435.1		c.-160+2298T>A		intron	N/A	ENSP00000506665.1	Q5ST81

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15251 AN: 151846 Hom.: 1179 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0843

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.100 AC: 15269 AN: 151964 Hom.: 1184 Cov.: 32 AF XY: 0.101 AC XY: 7503 AN XY: 74292

African (AFR) AF: 0.205 AC: 8482 AN: 41382

American (AMR) AF: 0.0795 AC: 1213 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0843 AC: 292 AN: 3464

East Asian (EAS) AF: 0.174 AC: 900 AN: 5162

South Asian (SAS) AF: 0.144 AC: 694 AN: 4806

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10590

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3192 AN: 67982

Other (OTH) AF: 0.110 AC: 232 AN: 2106

Alfa AF: 0.0677 Hom.: 69

Bravo AF: 0.111

Asia WGS AF: 0.188 AC: 651 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	-0.81
CADD	Benign	7.0
DANN	Benign	0.54
PhyloP100		0.48
PromoterAI		-0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9295910; hg19: chr6-30687714;