12-49128822-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006082.3(TUBA1B):​c.492G>A​(p.Lys164Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,589,318 control chromosomes in the GnomAD database, including 78,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10048 hom., cov: 30)
Exomes 𝑓: 0.34 ( 68764 hom. )

Consequence

TUBA1B
NM_006082.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.61
Variant links:
Genes affected
TUBA1B (HGNC:18809): (tubulin alpha 1b) Enables double-stranded RNA binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to act upstream of or within cellular response to interleukin-4. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 12-49128822-C-T is Benign according to our data. Variant chr12-49128822-C-T is described in ClinVar as [Benign]. Clinvar id is 1236526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.61 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TUBA1BNM_006082.3 linkuse as main transcriptc.492G>A p.Lys164Lys synonymous_variant 4/4 ENST00000336023.9 NP_006073.2 P68363-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TUBA1BENST00000336023.9 linkuse as main transcriptc.492G>A p.Lys164Lys synonymous_variant 4/41 NM_006082.3 ENSP00000336799.5 P68363-1

Frequencies

GnomAD3 genomes
AF:
0.355
AC:
53780
AN:
151292
Hom.:
10049
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.342
Gnomad AMI
AF:
0.219
Gnomad AMR
AF:
0.328
Gnomad ASJ
AF:
0.265
Gnomad EAS
AF:
0.713
Gnomad SAS
AF:
0.547
Gnomad FIN
AF:
0.381
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.333
Gnomad OTH
AF:
0.341
GnomAD3 exomes
AF:
0.356
AC:
85811
AN:
240850
Hom.:
14379
AF XY:
0.361
AC XY:
46936
AN XY:
129878
show subpopulations
Gnomad AFR exome
AF:
0.315
Gnomad AMR exome
AF:
0.314
Gnomad ASJ exome
AF:
0.241
Gnomad EAS exome
AF:
0.685
Gnomad SAS exome
AF:
0.477
Gnomad FIN exome
AF:
0.360
Gnomad NFE exome
AF:
0.302
Gnomad OTH exome
AF:
0.337
GnomAD4 exome
AF:
0.336
AC:
482453
AN:
1437908
Hom.:
68764
Cov.:
88
AF XY:
0.340
AC XY:
243308
AN XY:
715188
show subpopulations
Gnomad4 AFR exome
AF:
0.317
Gnomad4 AMR exome
AF:
0.321
Gnomad4 ASJ exome
AF:
0.259
Gnomad4 EAS exome
AF:
0.691
Gnomad4 SAS exome
AF:
0.490
Gnomad4 FIN exome
AF:
0.375
Gnomad4 NFE exome
AF:
0.312
Gnomad4 OTH exome
AF:
0.342
GnomAD4 genome
AF:
0.355
AC:
53796
AN:
151410
Hom.:
10048
Cov.:
30
AF XY:
0.362
AC XY:
26787
AN XY:
73924
show subpopulations
Gnomad4 AFR
AF:
0.342
Gnomad4 AMR
AF:
0.328
Gnomad4 ASJ
AF:
0.265
Gnomad4 EAS
AF:
0.713
Gnomad4 SAS
AF:
0.547
Gnomad4 FIN
AF:
0.381
Gnomad4 NFE
AF:
0.333
Gnomad4 OTH
AF:
0.339
Alfa
AF:
0.323
Hom.:
2094
Bravo
AF:
0.348

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 27, 2020- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
7.7
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs1057548; hg19: chr12-49522605; COSMIC: COSV60136316; COSMIC: COSV60136316; API