Variant rs3917187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003239.5(TGFB3):c.647-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 970,456 control chromosomes in the GnomAD database, including 259,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.65 ( 34307 hom., cov: 31)

Exomes 𝑓: 0.74 ( 224765 hom. )

Consequence

TGFB3
NM_003239.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.53

Variant links:

Genes affected

TGFB3 (HGNC:11769): (transforming growth factor beta 3) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]

TGFB3 links:

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IFT43 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 14-75965793-T-C is Benign according to our data. Variant chr14-75965793-T-C is described in ClinVar as [Benign]. Clinvar id is 1231224.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-75965793-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TGFB3	NM_003239.5 linkuse as main transcript	c.647-98A>G	intron_variant	ENST00000238682.8
TGFB3	NM_001329938.2 linkuse as main transcript	c.647-98A>G	intron_variant
TGFB3	NM_001329939.2 linkuse as main transcript	c.647-98A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB3	ENST00000238682.8 linkuse as main transcript	c.647-98A>G		intron_variant		1	NM_003239.5	P1	P10600-1

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99244

AN:

151952

Hom.:

34307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.747

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.690

Gnomad FIN

AF:

0.789

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.676

GnomAD4 exome

AF:

0.737

AC:

603180

AN:

818386

Hom.:

224765

Cov.:

AF XY:

0.737

AC XY:

319056

AN XY:

433098

show subpopulations

Gnomad4 AFR exome

AF:

0.413

Gnomad4 AMR exome

AF:

0.753

Gnomad4 ASJ exome

AF:

0.743

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.697

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.765

Gnomad4 OTH exome

AF:

0.723

GnomAD4 genome

AF:

0.653

AC:

99253

AN:

152070

Hom.:

34307

Cov.:

AF XY:

0.655

AC XY:

48701

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.701

Gnomad4 ASJ

AF:

0.747

Gnomad4 EAS

AF:

0.545

Gnomad4 SAS

AF:

0.690

Gnomad4 FIN

AF:

0.789

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.671

Alfa

AF:

0.717

Hom.:

9121

Bravo

AF:

0.638

Asia WGS

AF:

0.598

AC:

2079

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.010

DANN

Benign

0.31

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