Variant 20-59019435-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_030773.4(TUBB1):c.-88G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,501,846 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0084 ( 8 hom., cov: 33)

Exomes 𝑓: 0.014 ( 175 hom. )

Consequence

TUBB1
NM_030773.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.317

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00836 (1274/152334) while in subpopulation SAS AF= 0.0205 (99/4824). AF 95% confidence interval is 0.0173. There are 8 homozygotes in gnomad4. There are 573 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 1274 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
TUBB1	NM_030773.4 linkuse as main transcript	c.-88G>C	5_prime_UTR_premature_start_codon_gain_variant	1/4	ENST00000217133.2	NP_110400.1	Q9H4B7
TUBB1	NM_030773.4 linkuse as main transcript	c.-88G>C	5_prime_UTR_variant	1/4	ENST00000217133.2	NP_110400.1	Q9H4B7
TUBB1	XM_017028085.2 linkuse as main transcript	c.-10+2890G>C	intron_variant			XP_016883574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB1	ENST00000217133 linkuse as main transcript	c.-88G>C		5_prime_UTR_premature_start_codon_gain_variant	1/4	1	NM_030773.4	ENSP00000217133.1		Q9H4B7
TUBB1	ENST00000217133 linkuse as main transcript	c.-88G>C		5_prime_UTR_variant	1/4	1	NM_030773.4	ENSP00000217133.1		Q9H4B7

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1274

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00334

GnomAD4 exome

AF:

0.0136

AC:

18302

AN:

1349512

Hom.:

175

Cov.:

AF XY:

0.0138

AC XY:

9384

AN XY:

677650

show subpopulations

Gnomad4 AFR exome

AF:

0.00201

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.00950

Gnomad4 NFE exome

AF:

0.0152

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00836

AC:

1274

AN:

152334

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

573

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00305

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00757

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Macrothrombocytopenia, isolated, 1, autosomal dominant

Uncertain:1

Uncertain significance, no assertion criteria provided

research

ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.3

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over