rs6070696

Variant names:

• chr20-59022590-A-G
• rs6070696
• NM_030773.4:c.58-255A>G

Variant summary

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

The NM_030773.4(TUBB1):​c.58-255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,154 control chromosomes in the GnomAD database, including 2,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2641 hom., cov: 32)
• Consequence: TUBB1 NM_030773.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.333
• Publications: 10 publications found

Genes affected

TUBB1 (HGNC:16257): (tubulin beta 1 class VI) This gene encodes a member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is specifically expressed in platelets and megakaryocytes and may be involved in proplatelet production and platelet release. A mutations in this gene is associated with autosomal dominant macrothrombocytopenia. Two pseudogenes of this gene are found on chromosome Y.[provided by RefSeq, Jul 2010]

TUBB1 Gene-Disease associations (from GenCC):

• macrothrombocytopenia, isolated, 1, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal dominant macrothrombocytopenia

  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=-0.88).
• BP6: Variant 20-59022590-A-G is Benign according to our data. Variant chr20-59022590-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227387.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030773.4. 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
	TUBB1	NM_030773.4	MANE Select	c.58-255A>G		intron	N/A	NP_110400.1	Q9H4B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB1	ENST00000217133.2	TSL:1 MANE Select	c.58-255A>G		intron	N/A	ENSP00000217133.1	Q9H4B7

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27711 AN: 152036 Hom.: 2639 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.182 AC: 27732 AN: 152154 Hom.: 2641 Cov.: 32 AF XY: 0.188 AC XY: 14010 AN XY: 74394

African (AFR) AF: 0.174 AC: 7223 AN: 41502

American (AMR) AF: 0.160 AC: 2453 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.110 AC: 569 AN: 5180

South Asian (SAS) AF: 0.175 AC: 844 AN: 4820

European-Finnish (FIN) AF: 0.290 AC: 3067 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12490 AN: 68012

Other (OTH) AF: 0.171 AC: 362 AN: 2116

Alfa AF: 0.186 Hom.: 1873

Bravo AF: 0.171

Asia WGS AF: 0.139 AC: 485 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	-0.88
CADD	Benign	3.3
DANN	Benign	0.50
PhyloP100		0.33
Mutation Taster		=100/0	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: rs6070696; hg19: chr20-57597645; COSMIC: COSV53886224; COSMIC: COSV53886224;