9-99105255-TGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGC

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004612.4(TGFBR1):c.76_78delGCG(p.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 0.0017 in 1,041,918 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 18 hom., cov: 30)

Exomes 𝑓: 0.00084 ( 6 hom. )

Consequence

TGFBR1
NM_004612.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

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]

TGFBR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-99105255-TGGC-T is Benign according to our data. Variant chr9-99105255-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 213863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-99105255-TGGC-T is described in Lovd as [Benign]. Variant chr9-99105255-TGGC-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00714 (1017/142520) while in subpopulation AFR AF= 0.0241 (948/39326). AF 95% confidence interval is 0.0228. There are 18 homozygotes in gnomad4. There are 498 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1017 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR1	NM_004612.4 link	c.76_78delGCG	p.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
TGFBR1	ENST00000374994.9 link	c.76_78delGCG	p.Ala26del	conservative_inframe_deletion	Exon 1 of 9	1	NM_004612.4	ENSP00000364133.4		P36897-1

Frequencies

GnomAD3 genomes

AF:

0.00703

AC:

1001

AN:

142418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00296

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00174

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00694

Gnomad NFE

AF:

0.0000774

Gnomad OTH

AF:

0.00612

GnomAD3 exomes

AF:

0.00514

AC:

AN:

584

Hom.:

AF XY:

0.00588

AC XY:

AN XY:

340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00493

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000841

AC:

756

AN:

899398

Hom.:

AF XY:

0.000996

AC XY:

420

AN XY:

421838

show subpopulations

Gnomad4 AFR exome

AF:

0.0205

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.000274

Gnomad4 EAS exome

AF:

0.00142

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.00254

Gnomad4 NFE exome

AF:

0.000337

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00714

AC:

1017

AN:

142520

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

498

AN XY:

69398

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00152

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000774

Gnomad4 OTH

AF:

0.00605

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

May 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 18, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TGFBR1: BP3, BS1, BS2 -

not specified

Benign:3

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 10, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:3

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 03, 2018

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. -

Apr 11, 2018

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Apr 01, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over