Genetic Variant TGFBRAP1:c.*1239G>A (chr2-105266144-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004257.6(TGFBRAP1):c.*1239G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,178 control chromosomes in the GnomAD database, including 3,267 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 0.19 ( 3267 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TGFBRAP1
NM_004257.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.874

Publications

1 publications found

Variant links:

Genes affected

TGFBRAP1 (HGNC:16836): (transforming growth factor beta receptor associated protein 1) This gene encodes a protein that binds to transforming growth factor-beta (TGF-beta) receptors and plays a role in TGF-beta signaling. The encoded protein acts as a chaprone in signaling downstream of TGF-beta. It is involved in signal-dependent association with SMAD4. The protein is also a component of mammalian CORVET, a multisubunit tethering protein complex that is involved in fusion of early endosomes. [provided by RefSeq, Jun 2016]

TGFBRAP1 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6 link	c.*1239G>A	3_prime_UTR_variant	Exon 12 of 12	ENST00000393359.7	NP_004248.2	Q8WUH2
TGFBRAP1	NM_001142621.3 link	c.*1239G>A	3_prime_UTR_variant	Exon 12 of 12		NP_001136093.1	Q8WUH2
TGFBRAP1	NM_001328646.3 link	c.2406+3128G>A	intron_variant	Intron 11 of 11		NP_001315575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7 link	c.*1239G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_004257.6	ENSP00000377027.2		Q8WUH2
TGFBRAP1	ENST00000595531.5 link	c.*1239G>A		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000471434.2		Q8WUH2

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28188

AN:

152060

Hom.:

3267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.0661

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.181

GnomAD2 exomes

AF:

0.143

AC:

AN:

AF XY:

0.250

show subpopulations

Gnomad ASJ exome

AF:

0.500

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.100

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.185

AC:

28209

AN:

152178

Hom.:

3267

Cov.:

AF XY:

0.189

AC XY:

14046

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.259

AC:

10767

AN:

41514

American (AMR)

AF:

0.197

AC:

3009

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

440

AN:

3472

East Asian (EAS)

AF:

0.513

AC:

2646

AN:

5160

South Asian (SAS)

AF:

0.234

AC:

1127

AN:

4818

European-Finnish (FIN)

AF:

0.131

AC:

1395

AN:

10616

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8324

AN:

67990

Other (OTH)

AF:

0.188

AC:

397

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1136

2272

3407

4543

5679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.170

Hom.:

342

Bravo

AF:

0.196

Asia WGS

AF:

0.363

AC:

1260

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.52

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over