ENST00000597453.1:n.375delC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000597453.1(TGFB1):n.375delC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,614,128 control chromosomes in the GnomAD database, including 213 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 20 hom., cov: 31)

Exomes 𝑓: 0.015 ( 193 hom. )

Consequence

TGFB1
ENST00000597453.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.563

Publications

19 publications found

Variant links:

Genes affected

TGFB1 (HGNC:11766): (transforming growth factor beta 1) 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 TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]

TGFB1 Gene-Disease associations (from GenCC):

Camurati-Engelmann disease
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
inflammatory bowel disease, immunodeficiency, and encephalopathy
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TGFB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 19-41342037-TG-T is Benign according to our data. Variant chr19-41342037-TG-T is described in ClinVar as Benign. ClinVar VariationId is 197687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.011 (1669/152248) while in subpopulation NFE AF = 0.0175 (1189/68010). AF 95% confidence interval is 0.0167. There are 20 homozygotes in GnomAd4. There are 813 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB1	NM_000660.7 link	c.713-8delC		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000221930.6	NP_000651.3	P01137A0A499FJK2
TGFB1	XM_011527242.3 link	c.713-5delC		splice_region_variant, intron_variant	Intron 4 of 6		XP_011525544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB1	ENST00000221930.6 link	c.713-8delC		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_000660.7	ENSP00000221930.4		A0A499FJK2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1670

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00767

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0128

AC:

3207

AN:

251012

AF XY:

0.0132

show subpopulations

Gnomad AFR exome

AF:

0.00253

Gnomad AMR exome

AF:

0.00584

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0149

AC:

21784

AN:

1461880

Hom.:

193

Cov.:

AF XY:

0.0148

AC XY:

10763

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00239

AC:

AN:

33480

American (AMR)

AF:

0.00595

AC:

266

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

267

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00674

AC:

581

AN:

86256

European-Finnish (FIN)

AF:

0.0148

AC:

790

AN:

53420

Middle Eastern (MID)

AF:

0.0499

AC:

288

AN:

5768

European-Non Finnish (NFE)

AF:

0.0168

AC:

18696

AN:

1112002

Other (OTH)

AF:

0.0134

AC:

812

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1427

2854

4281

5708

7135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.0110

AC:

1669

AN:

152248

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

813

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00270

AC:

112

AN:

41546

American (AMR)

AF:

0.00766

AC:

117

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.00477

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10616

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1189

AN:

68010

Other (OTH)

AF:

0.0152

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0160

Hom.:

Bravo

AF:

0.00992

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0180

EpiControl

AF:

0.0187

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 18, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism

(source)

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

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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