Variant rs7871490 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004612.4(TGFBR1):c.*2103T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 222,492 control chromosomes in the GnomAD database, including 1,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.13 ( 1427 hom., cov: 28)

Exomes 𝑓: 0.13 ( 499 hom. )

Consequence

TGFBR1
NM_004612.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: -0.212

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBR1	NM_004612.4 linkuse as main transcript	c.*2103T>G		3_prime_UTR_variant	9/9	ENST00000374994.9	NP_004603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR1	ENST00000374994.9 linkuse as main transcript	c.*2103T>G		3_prime_UTR_variant	9/9	1	NM_004612.4	ENSP00000364133	P4	P36897-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19146

AN:

148010

Hom.:

1422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.0913

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.110

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.127

AC:

9489

AN:

74444

Hom.:

499

Cov.:

AF XY:

0.127

AC XY:

4357

AN XY:

34368

show subpopulations

Gnomad4 AFR exome

AF:

0.0624

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0200

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.129

AC:

19156

AN:

148048

Hom.:

1427

Cov.:

AF XY:

0.132

AC XY:

9494

AN XY:

71988

show subpopulations

Gnomad4 AFR

AF:

0.0573

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0204

Gnomad4 SAS

AF:

0.0914

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.169

Hom.:

197

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Loeys-Dietz syndrome 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Familial thoracic aortic aneurysm and aortic dissection

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Loeys-Dietz syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.81

DANN

Benign

0.17

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