Variant 1-91720237-AAAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003243.5(TGFBR3):c.1076-10_1076-8delCTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,576,342 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 4 hom. )

Consequence

TGFBR3
NM_003243.5 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.329

Variant links:

Genes affected

TGFBR3 (HGNC:11774): (transforming growth factor beta receptor 3) This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

TGFBR3 links:

TGFBR3 (HGNC:):

TGFBR3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-91720237-AAAG-A is Benign according to our data. Variant chr1-91720237-AAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 547817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 167 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR3	NM_003243.5 linkuse as main transcript	c.1076-10_1076-8delCTT		splice_region_variant, intron_variant		ENST00000212355.9	NP_003234.2	Q03167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 linkuse as main transcript	c.1076-10_1076-8delCTT		splice_region_variant, intron_variant		1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000859

AC:

157

AN:

182668

Hom.:

AF XY:

0.000724

AC XY:

AN XY:

98018

show subpopulations

Gnomad AFR exome

AF:

0.000362

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00143

GnomAD4 exome

AF:

0.00119

AC:

1692

AN:

1423998

Hom.:

AF XY:

0.00111

AC XY:

782

AN XY:

705030

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000118

Gnomad4 NFE exome

AF:

0.00141

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152344

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00105

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

TGFBR3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2019

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). -

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Jun 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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