18-49507-G-C

Position:

• chr18-49507-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001358689.2(TUBB8B):​c.51C>G​(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 146,130 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (6 hom., cov: 25)
  • Exomes 𝑓: 0.00034 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBB8B NM_001358689.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.00

Genes affected

TUBB8B (HGNC:24983): (tubulin beta 8B) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TUBB8B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-49507-G-C is Benign according to our data. Variant chr18-49507-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2648510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-9 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8B	NM_001358689.2	c.51C>G	p.Gly17Gly	synonymous_variant	1/4	ENST00000308911.9	NP_001345618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB8B	ENST00000308911.9	c.51C>G	p.Gly17Gly	synonymous_variant	1/4	6	NM_001358689.2	ENSP00000496713.1
TUBB8B	ENST00000706408.1	n.1019+220C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 426 AN: 146028 Hom.: 6 Cov.: 25

Gnomad AFR AF: 0.00988

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000744

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000217

Gnomad SAS AF: 0.000225

Gnomad FIN AF: 0.000498

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000197

Gnomad OTH AF: 0.00152

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000345 AC: 275 AN: 797312 Hom.: 3 Cov.: 12 AF XY: 0.000335 AC XY: 138 AN XY: 412340

Gnomad4 AFR exome AF: 0.00580

Gnomad4 AMR exome AF: 0.000471

Gnomad4 ASJ exome AF: 0.0000999

Gnomad4 EAS exome AF: 0.0000956

Gnomad4 SAS exome AF: 0.000230

Gnomad4 FIN exome AF: 0.0000442

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.000506

GnomAD4 genome AF: 0.00293 AC: 428 AN: 146130 Hom.: 6 Cov.: 25 AF XY: 0.00298 AC XY: 212 AN XY: 71136

Gnomad4 AFR AF: 0.00990

Gnomad4 AMR AF: 0.000744

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000217

Gnomad4 SAS AF: 0.000225

Gnomad4 FIN AF: 0.000498

Gnomad4 NFE AF: 0.000197

Gnomad4 OTH AF: 0.00150

Alfa AF: 0.000794 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TUBB8B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752264814; hg19: chr18-49507;