rs6070696

Positions:

• chr20-59022590-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB1	NM_030773.4	c.58-255A>G		intron_variant		ENST00000217133.2	NP_110400.1
TUBB1	XM_017028085.2	c.-9-255A>G		intron_variant			XP_016883574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB1	ENST00000217133.2	c.58-255A>G		intron_variant		1	NM_030773.4	ENSP00000217133	P1

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.171

Alfa AF: 0.184 Hom.: 1370

Bravo AF: 0.171

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs6070696; hg19: chr20-57597645; COSMIC: COSV53886224; COSMIC: COSV53886224;