chr9-99105255-TGGCGGC-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_004612.4(TGFBR1):​c.73_78delGCGGCG​(p.Ala25_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 0.0000441 in 1,043,466 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

TGFBR1
NM_004612.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.84
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6
Variant 9-99105255-TGGCGGC-T is Benign according to our data. Variant chr9-99105255-TGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 263873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFBR1NM_004612.4 linkc.73_78delGCGGCG p.Ala25_Ala26del conservative_inframe_deletion Exon 1 of 9 ENST00000374994.9 NP_004603.1 P36897-1Q5T7S2B4DXN7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFBR1ENST00000374994.9 linkc.73_78delGCGGCG p.Ala25_Ala26del conservative_inframe_deletion Exon 1 of 9 1 NM_004612.4 ENSP00000364133.4 P36897-1

Frequencies

GnomAD3 genomes
AF:
0.0000702
AC:
10
AN:
142424
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000255
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000688
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000413
Gnomad SAS
AF:
0.000217
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00347
Gnomad NFE
AF:
0.0000619
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000400
AC:
36
AN:
900942
Hom.:
0
AF XY:
0.0000402
AC XY:
17
AN XY:
422746
show subpopulations
Gnomad4 AFR exome
AF:
0.000345
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000137
Gnomad4 EAS exome
AF:
0.000109
Gnomad4 SAS exome
AF:
0.000111
Gnomad4 FIN exome
AF:
0.000194
Gnomad4 NFE exome
AF:
0.0000272
Gnomad4 OTH exome
AF:
0.0000958
GnomAD4 genome
AF:
0.0000702
AC:
10
AN:
142524
Hom.:
0
Cov.:
30
AF XY:
0.000101
AC XY:
7
AN XY:
69398
show subpopulations
Gnomad4 AFR
AF:
0.0000254
Gnomad4 AMR
AF:
0.0000687
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000415
Gnomad4 SAS
AF:
0.000217
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000619
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:3
Mar 19, 2015
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Dec 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 14, 2019
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

TGFBR1-related disorder Benign:1
Sep 13, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
May 08, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs11466445; hg19: chr9-101867537; API