chr9-137241427-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006088.6(TUBB4B):​c.57+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,582,252 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 9 hom. )

Consequence

TUBB4B
NM_006088.6 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.35
Variant links:
Genes affected
TUBB4B (HGNC:20771): (tubulin beta 4B class IVb) Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. Implicated in Leber congenital amaurosis with early-onset deafness. [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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 9-137241427-C-T is Benign according to our data. Variant chr9-137241427-C-T is described in ClinVar as [Benign]. Clinvar id is 1552996.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000571 (817/1430112) while in subpopulation EAS AF= 0.0202 (722/35784). AF 95% confidence interval is 0.019. There are 9 homozygotes in gnomad4_exome. There are 398 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TUBB4BNM_006088.6 linkc.57+10C>T intron_variant Intron 1 of 3 ENST00000340384.5 NP_006079.1 P68371

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TUBB4BENST00000340384.5 linkc.57+10C>T intron_variant Intron 1 of 3 1 NM_006088.6 ENSP00000341289.4 P68371
TUBB4BENST00000604929.1 linkn.130+10C>T intron_variant Intron 1 of 2 1

Frequencies

GnomAD3 genomes
AF:
0.000335
AC:
51
AN:
152026
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00810
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000795
AC:
165
AN:
207622
Hom.:
1
AF XY:
0.000618
AC XY:
72
AN XY:
116460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0113
Gnomad SAS exome
AF:
0.0000354
Gnomad FIN exome
AF:
0.0000596
Gnomad NFE exome
AF:
0.0000641
Gnomad OTH exome
AF:
0.000604
GnomAD4 exome
AF:
0.000571
AC:
817
AN:
1430112
Hom.:
9
Cov.:
31
AF XY:
0.000559
AC XY:
398
AN XY:
711836
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0202
Gnomad4 SAS exome
AF:
0.0000593
Gnomad4 FIN exome
AF:
0.0000211
Gnomad4 NFE exome
AF:
0.0000637
Gnomad4 OTH exome
AF:
0.000288
GnomAD4 genome
AF:
0.000329
AC:
50
AN:
152140
Hom.:
0
Cov.:
33
AF XY:
0.000390
AC XY:
29
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00792
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000371
Hom.:
0
Bravo
AF:
0.000280

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 19, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
3.2
DANN
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs201085838; hg19: chr9-140135879; API