rs11466445
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-T
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
- chr9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2
The NM_004612.4(TGFBR1):c.61_78delGCGGCGGCGGCGGCGGCG(p.Ala21_Ala26del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,043,392 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TGFBR1
NM_004612.4 conservative_inframe_deletion
NM_004612.4 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.84
Publications
24 publications found
Genes affected
TGFBR1 (HGNC:11772): (transforming growth factor beta receptor 1) The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
TGFBR1 Gene-Disease associations (from GenCC):
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Loeys-Dietz syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Loeys-Dietz syndrome 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- multiple self-healing squamous epitheliomaInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_004612.4
BS1
Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000144 (13/900968) while in subpopulation SAS AF = 0.000554 (10/18064). AF 95% confidence interval is 0.0003. There are 0 homozygotes in GnomAdExome4. There are 9 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAdExome4 at 13 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004612.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TGFBR1 | MANE Select | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 9 | NP_004603.1 | P36897-1 | ||
| TGFBR1 | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 9 | NP_001293139.1 | P36897-2 | |||
| TGFBR1 | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 8 | NP_001394345.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TGFBR1 | TSL:1 MANE Select | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 9 | ENSP00000364133.4 | P36897-1 | ||
| TGFBR1 | TSL:1 | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 9 | ENSP00000447297.1 | P36897-2 | ||
| TGFBR1 | TSL:1 | c.61_78delGCGGCGGCGGCGGCGGCG | p.Ala21_Ala26del | conservative_inframe_deletion | Exon 1 of 8 | ENSP00000364129.2 | P36897-3 |
Frequencies
GnomAD3 genomes 0.00000702 AC: 1AN: 142424Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
142424
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000144 AC: 13AN: 900968Hom.: 0 AF XY: 0.0000213 AC XY: 9AN XY: 422762 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
900968
Hom.:
AF XY:
AC XY:
9
AN XY:
422762
show subpopulations
African (AFR)
AF:
AC:
0
AN:
17388
American (AMR)
AF:
AC:
0
AN:
2804
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
7300
East Asian (EAS)
AF:
AC:
0
AN:
9216
South Asian (SAS)
AF:
AC:
10
AN:
18064
European-Finnish (FIN)
AF:
AC:
0
AN:
5144
Middle Eastern (MID)
AF:
AC:
0
AN:
1952
European-Non Finnish (NFE)
AF:
AC:
2
AN:
807768
Other (OTH)
AF:
AC:
1
AN:
31332
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.421
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 0.00000702 AC: 1AN: 142424Hom.: 0 Cov.: 30 AF XY: 0.0000144 AC XY: 1AN XY: 69286 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
142424
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
69286
show subpopulations
African (AFR)
AF:
AC:
0
AN:
39216
American (AMR)
AF:
AC:
0
AN:
14538
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3342
East Asian (EAS)
AF:
AC:
0
AN:
4840
South Asian (SAS)
AF:
AC:
1
AN:
4610
European-Finnish (FIN)
AF:
AC:
0
AN:
8144
Middle Eastern (MID)
AF:
AC:
0
AN:
288
European-Non Finnish (NFE)
AF:
AC:
0
AN:
64632
Other (OTH)
AF:
AC:
0
AN:
1962
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<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:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
1
-
Familial thoracic aortic aneurysm and aortic dissection (1)
-
1
-
Multiple self-healing squamous epithelioma;C4551955:Loeys-Dietz syndrome 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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