18-48992-A-G

Position:

• chr18-48992-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001389610.1(TUBB8B):​c.149T>C​(p.Leu50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000027 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUBB8B NM_001389610.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.65

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 18-48992-A-G is Benign according to our data. Variant chr18-48992-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2648508.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUBB8B	NM_001358689.2	c.225T>C	p.Ser75Ser	synonymous_variant	3/4	ENST00000308911.9	NP_001345618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUBB8B	ENST00000308911.9	c.225T>C	p.Ser75Ser	synonymous_variant	3/4	6	NM_001358689.2	ENSP00000496713.1
TUBB8B	ENST00000706408.1	n.1187T>C		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 60 AN: 146990 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000826

Gnomad AMI AF: 0.00233

Gnomad AMR AF: 0.000746

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000592

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.000500

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000268 AC: 39 AN: 1454596 Hom.: 2 Cov.: 32 AF XY: 0.0000249 AC XY: 18 AN XY: 723796

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.0000334

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000422 AC: 62 AN: 147090 Hom.: 0 Cov.: 31 AF XY: 0.000488 AC XY: 35 AN XY: 71736

Gnomad4 AFR AF: 0.000875

Gnomad4 AMR AF: 0.000745

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000592

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.000495

Alfa AF: 0.000474 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

Jan 01, 2023

TUBB8B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.4
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs751460900; hg19: chr18-48992;