Genetic Variant ENST00000305253.8:c.204-21158T>C (chr11-8068452-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000305253.8(TUB):c.204-21158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,160 control chromosomes in the GnomAD database, including 16,271 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16244 hom., cov: 32)

Exomes 𝑓: 0.48 ( 27 hom. )

Consequence

TUB
ENST00000305253.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.434

Publications

3 publications found

Variant links:

Genes affected

TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

TUB links:

TUB-AS1 (HGNC:51120): (TUB antisense RNA 1)

TUB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TUB-AS1	NR_120537.1 link	n.1100T>C	non_coding_transcript_exon_variant	Exon 4 of 4
TUB-AS1	NR_120538.1 link	n.1043T>C	non_coding_transcript_exon_variant	Exon 3 of 3
TUB	NM_003320.5 link	c.204-21158T>C	intron_variant	Intron 2 of 12	NP_003311.2	P50607-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TUB	ENST00000305253.8 link	c.204-21158T>C	intron_variant	Intron 2 of 12	1	ENSP00000305426.4	P50607-2
TUB-AS1	ENST00000506601.1 link	n.1100T>C	non_coding_transcript_exon_variant	Exon 4 of 4	2
TUB	ENST00000534099.5 link	c.57-21158T>C	intron_variant	Intron 1 of 11	2	ENSP00000434400.1	E9PQR4

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69383

AN:

151830

Hom.:

16241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.481

AC:

102

AN:

212

Hom.:

Cov.:

AF XY:

0.473

AC XY:

AN XY:

146

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.513

AC:

AN:

154

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

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

AF:

0.457

AC:

69405

AN:

151948

Hom.:

16244

Cov.:

AF XY:

0.451

AC XY:

33500

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.527

AC:

21834

AN:

41428

American (AMR)

AF:

0.334

AC:

5097

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3470

East Asian (EAS)

AF:

0.461

AC:

2373

AN:

5150

South Asian (SAS)

AF:

0.472

AC:

2271

AN:

4816

European-Finnish (FIN)

AF:

0.464

AC:

4908

AN:

10574

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30357

AN:

67936

Other (OTH)

AF:

0.418

AC:

879

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1932

3864

5796

7728

9660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.444

Hom.:

64048

Bravo

AF:

0.452

Asia WGS

AF:

0.446

AC:

1549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.0

(source)

DANN

Benign

0.70

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over