Variant rs199547345 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_178012.5(TUBB2B):c.718C>T(p.Leu240Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,606,512 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 27)

Exomes 𝑓: 0.016 ( 203 hom. )

Consequence

TUBB2B
NM_178012.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

TUBB2B (HGNC:30829): (tubulin beta 2B class IIb) The protein encoded by this gene is a beta isoform of tubulin, which binds GTP and is a major component of microtubules. This gene is highly similar to TUBB2A and TUBB2C. Defects in this gene are a cause of asymmetric polymicrogyria. [provided by RefSeq, Mar 2010]

TUBB2B links:

TUBB2B (HGNC:):

TUBB2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-3225371-G-A is Benign according to our data. Variant chr6-3225371-G-A is described in ClinVar as [Benign]. Clinvar id is 160185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-3225371-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0125 (1814/145128) while in subpopulation NFE AF= 0.0196 (1281/65390). AF 95% confidence interval is 0.0187. There are 15 homozygotes in gnomad4. There are 811 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1814 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB2B	NM_178012.5 linkuse as main transcript	c.718C>T	p.Leu240Leu	synonymous_variant	4/4	ENST00000259818.8	NP_821080.1	Q9BVA1A0A384MEE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB2B	ENST00000259818.8 linkuse as main transcript	c.718C>T	p.Leu240Leu	synonymous_variant	4/4	1	NM_178012.5	ENSP00000259818.6		Q9BVA1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1815

AN:

145036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00114

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0212

Gnomad EAS

AF:

0.000423

Gnomad SAS

AF:

0.00396

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0662

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0221

GnomAD3 exomes

AF:

0.0119

AC:

1876

AN:

158160

Hom.:

AF XY:

0.0123

AC XY:

1056

AN XY:

86160

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00779

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00315

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0157

AC:

23013

AN:

1461384

Hom.:

203

Cov.:

AF XY:

0.0158

AC XY:

11500

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.00827

Gnomad4 ASJ exome

AF:

0.0231

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0125

AC:

1814

AN:

145128

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

811

AN XY:

70220

show subpopulations

Gnomad4 AFR

AF:

0.00289

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0212

Gnomad4 EAS

AF:

0.000424

Gnomad4 SAS

AF:

0.00397

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0219

Alfa

AF:

0.0159

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 06, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.46

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