dbSNP rs751460900: TUBB8B:p.Ser75Ser (chr18-48992-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.65

Publications

0 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2648508.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389610.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBB8B	NM_001358689.2	MANE Select	c.225T>C	p.Ser75Ser	synonymous	Exon 3 of 4	NP_001345618.1	A6NNZ2
TUBB8B	NM_001389610.1		c.149T>C	p.Leu50Pro	missense	Exon 5 of 7	NP_001376539.1
TUBB8B	NM_001389609.1		c.9T>C	p.Ser3Ser	synonymous	Exon 5 of 6	NP_001376538.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBB8B	ENST00000308911.9	TSL:6 MANE Select	c.225T>C	p.Ser75Ser	synonymous	Exon 3 of 4	ENSP00000496713.1	A6NNZ2
TUBB8B	ENST00000706408.1		n.1187T>C		non_coding_transcript_exon	Exon 4 of 5
TUBB8B	ENST00000594555.1	TSL:3	n.-110T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

146990

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249964

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000268

AC:

AN:

1454596

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

723796

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000123

AC:

AN:

32638

American (AMR)

AF:

0.000157

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39602

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4316

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1108568

Other (OTH)

AF:

0.0000334

AC:

AN:

59914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.309

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000422

AC:

AN:

147090

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

AN XY:

71736

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000875

AC:

AN:

38846

American (AMR)

AF:

0.000745

AC:

AN:

14766

Ashkenazi Jewish (ASJ)

AF:

0.000294

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4672

European-Finnish (FIN)

AF:

0.000592

AC:

AN:

10130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67030

Other (OTH)

AF:

0.000495

AC:

AN:

2022

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000474

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.4

(source)

DANN

Benign

0.44

PhyloP100

-3.7

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over