ENST00000556285.1:c.*100G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000556285.1(TGFB3):c.*100G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,249,846 control chromosomes in the GnomAD database, including 346,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38508 hom., cov: 30)

Exomes 𝑓: 0.75 ( 307500 hom. )

Consequence

TGFB3
ENST00000556285.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

cranioectodermal dysplasia 3
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
short-rib thoracic dysplasia 18 with polydactyly
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cranioectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
retinitis pigmentosa 81
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

IFT43 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 14-75963212-C-T is Benign according to our data. Variant chr14-75963212-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGFB3	NM_003239.5 link	c.926+104G>A	intron_variant	Intron 5 of 6	ENST00000238682.8	NP_003230.1	P10600-1A5YM40B3KVH9
TGFB3	NM_001329938.2 link	c.*100G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001316867.1	P10600-2
TGFB3	NM_001329939.2 link	c.926+104G>A	intron_variant	Intron 6 of 7		NP_001316868.1	P10600-1A5YM40

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB3	ENST00000238682.8 link	c.926+104G>A		intron_variant	Intron 5 of 6	1	NM_003239.5	ENSP00000238682.3		P10600-1

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

107317

AN:

151872

Hom.:

38496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.711

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.790

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.764

Gnomad OTH

AF:

0.711

GnomAD4 exome

AF:

0.745

AC:

818096

AN:

1097856

Hom.:

307500

Cov.:

AF XY:

0.745

AC XY:

419120

AN XY:

562220

show subpopulations

African (AFR)

AF:

0.606

AC:

16013

AN:

26432

American (AMR)

AF:

0.748

AC:

32541

AN:

43482

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

17834

AN:

23864

East Asian (EAS)

AF:

0.497

AC:

18825

AN:

37840

South Asian (SAS)

AF:

0.735

AC:

57544

AN:

78324

European-Finnish (FIN)

AF:

0.784

AC:

41453

AN:

52860

Middle Eastern (MID)

AF:

0.710

AC:

2577

AN:

3630

European-Non Finnish (NFE)

AF:

0.761

AC:

595808

AN:

783050

Other (OTH)

AF:

0.734

AC:

35501

AN:

48374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10935

21871

32806

43742

54677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12044

24088

36132

48176

60220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.706

AC:

107363

AN:

151990

Hom.:

38508

Cov.:

AF XY:

0.707

AC XY:

52529

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.604

AC:

25008

AN:

41424

American (AMR)

AF:

0.711

AC:

10866

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

2602

AN:

3470

East Asian (EAS)

AF:

0.511

AC:

2641

AN:

5164

South Asian (SAS)

AF:

0.727

AC:

3492

AN:

4806

European-Finnish (FIN)

AF:

0.790

AC:

8362

AN:

10580

Middle Eastern (MID)

AF:

0.736

AC:

215

AN:

292

European-Non Finnish (NFE)

AF:

0.764

AC:

51891

AN:

67954

Other (OTH)

AF:

0.704

AC:

1486

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1552

3103

4655

6206

7758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.742

Hom.:

28956

Bravo

AF:

0.698

Asia WGS

AF:

0.613

AC:

2133

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over