rs1054332

chr6-3225480-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_178012.5(TUBB2B):c.609C>T(p.Asp203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,612,216 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0040 (30 hom.)
• Consequence: TUBB2B NM_178012.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.993

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-3225480-G-A is Benign according to our data. Variant chr6-3225480-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-3225480-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.993 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00403 (5880/1460112) while in subpopulation MID AF= 0.0254 (146/5744). AF 95% confidence interval is 0.0221. There are 30 homozygotes in gnomad4_exome. There are 2999 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd at 621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUBB2B	NM_178012.5	c.609C>T	p.Asp203=	synonymous_variant	4/4	ENST00000259818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBB2B	ENST00000259818.8	c.609C>T	p.Asp203=	synonymous_variant	4/4	1	NM_178012.5	P1

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 621 AN: 151986 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00454

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00524

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.000906 AC: 224 AN: 247170 Hom.: 2 AF XY: 0.000805 AC XY: 108 AN XY: 134230

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.000603

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000622

Gnomad FIN exome AF: 0.000654

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.00403 AC: 5880 AN: 1460112 Hom.: 30 Cov.: 34 AF XY: 0.00413 AC XY: 2999 AN XY: 726380

Gnomad4 AFR exome AF: 0.00270

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00290

Gnomad4 FIN exome AF: 0.00324

Gnomad4 NFE exome AF: 0.00425

Gnomad4 OTH exome AF: 0.00476

GnomAD4 genome AF: 0.00410 AC: 623 AN: 152104 Hom.: 4 Cov.: 30 AF XY: 0.00391 AC XY: 291 AN XY: 74366

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00454

Gnomad4 NFE AF: 0.00524

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00553 Hom.: 2

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	TUBB2B: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 23, 2018	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 13, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Complex cortical dysplasia with other brain malformations 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	4.2
Dann	Benign	0.58

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: rs1054332; hg19: chr6-3225714;