Variant chr20-59022871-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030773.4(TUBB1):c.84C>T(p.His28His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,614,062 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 7 hom. )

Consequence

TUBB1
NM_030773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.14

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 20-59022871-C-T is Benign according to our data. Variant chr20-59022871-C-T is described in ClinVar as [Benign]. Clinvar id is 720416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00328 (499/152194) while in subpopulation AFR AF= 0.0114 (473/41494). AF 95% confidence interval is 0.0106. There are 1 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB1	NM_030773.4 linkuse as main transcript	c.84C>T	p.His28His	synonymous_variant	2/4	ENST00000217133.2	NP_110400.1	Q9H4B7
TUBB1	XM_017028085.2 linkuse as main transcript	c.18C>T	p.His6His	synonymous_variant	2/4		XP_016883574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB1	ENST00000217133.2 linkuse as main transcript	c.84C>T	p.His28His	synonymous_variant	2/4	1	NM_030773.4	ENSP00000217133.1		Q9H4B7

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

495

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000911

AC:

229

AN:

251424

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000406

AC:

594

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

231

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00328

AC:

499

AN:

152194

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00417

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.084

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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