rs1030877

Variant summary

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

The NM_004257.6(TGFBRAP1):​c.1038+2300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,002 control chromosomes in the GnomAD database, including 28,567 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 0.61 ( 28567 hom., cov: 32)

Consequence

TGFBRAP1
NM_004257.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

9 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]

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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=-0.94).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004257.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TGFBRAP1
NM_004257.6
MANE Select
c.1038+2300C>T
intron
N/ANP_004248.2
TGFBRAP1
NM_001142621.3
c.1038+2300C>T
intron
N/ANP_001136093.1
TGFBRAP1
NM_001328646.3
c.1038+2300C>T
intron
N/ANP_001315575.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TGFBRAP1
ENST00000393359.7
TSL:1 MANE Select
c.1038+2300C>T
intron
N/AENSP00000377027.2
TGFBRAP1
ENST00000595531.5
TSL:1
c.1038+2300C>T
intron
N/AENSP00000471434.2

Frequencies

GnomAD3 genomes
AF:
0.608
AC:
92358
AN:
151884
Hom.:
28544
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.586
Gnomad AMI
AF:
0.596
Gnomad AMR
AF:
0.626
Gnomad ASJ
AF:
0.579
Gnomad EAS
AF:
0.277
Gnomad SAS
AF:
0.522
Gnomad FIN
AF:
0.598
Gnomad MID
AF:
0.573
Gnomad NFE
AF:
0.652
Gnomad OTH
AF:
0.596
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.608
AC:
92443
AN:
152002
Hom.:
28567
Cov.:
32
AF XY:
0.601
AC XY:
44628
AN XY:
74294
show subpopulations
African (AFR)
AF:
0.587
AC:
24314
AN:
41448
American (AMR)
AF:
0.626
AC:
9564
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.579
AC:
2007
AN:
3468
East Asian (EAS)
AF:
0.278
AC:
1440
AN:
5174
South Asian (SAS)
AF:
0.525
AC:
2521
AN:
4806
European-Finnish (FIN)
AF:
0.598
AC:
6310
AN:
10560
Middle Eastern (MID)
AF:
0.565
AC:
166
AN:
294
European-Non Finnish (NFE)
AF:
0.652
AC:
44333
AN:
67958
Other (OTH)
AF:
0.590
AC:
1247
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1822
3643
5465
7286
9108
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
766
1532
2298
3064
3830
<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:
0.623
Hom.:
38560
Bravo
AF:
0.607
Asia WGS
AF:
0.434
AC:
1506
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.079
DANN
Benign
0.45
PhyloP100
-1.2
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1030877; hg19: chr2-105910513; API