Genetic Variant TGFBR3:n.*2522G>A (chr1-91683720-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000532540.5(TGFBR3):n.*2522G>A 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 0.17 in 1,406,694 control chromosomes in the GnomAD database, including 19,366 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1601 hom., cov: 32)

Exomes 𝑓: 0.17 ( 17765 hom. )

Consequence

TGFBR3
ENST00000532540.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122

Publications

7 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5 link	c.*19G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000212355.9	NP_003234.2	Q03167-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFBR3	ENST00000212355.9 link	c.*19G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

20695

AN:

145188

Hom.:

1597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.135

AC:

20295

AN:

150396

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.0920

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.173

AC:

218654

AN:

1261374

Hom.:

17765

Cov.:

AF XY:

0.173

AC XY:

107550

AN XY:

621954

show subpopulations

African (AFR)

AF:

0.0960

AC:

2651

AN:

27626

American (AMR)

AF:

0.107

AC:

3472

AN:

32488

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

3678

AN:

20556

East Asian (EAS)

AF:

0.161

AC:

4037

AN:

25074

South Asian (SAS)

AF:

0.110

AC:

8544

AN:

77760

European-Finnish (FIN)

AF:

0.226

AC:

5937

AN:

26262

Middle Eastern (MID)

AF:

0.205

AC:

742

AN:

3622

European-Non Finnish (NFE)

AF:

0.181

AC:

181194

AN:

998478

Other (OTH)

AF:

0.170

AC:

8399

AN:

49508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9760

19519

29279

39038

48798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6468

12936

19404

25872

32340

<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:

0.143

AC:

20713

AN:

145320

Hom.:

1601

Cov.:

AF XY:

0.142

AC XY:

10077

AN XY:

70826

show subpopulations

African (AFR)

AF:

0.0912

AC:

3667

AN:

40212

American (AMR)

AF:

0.127

AC:

1861

AN:

14634

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

467

AN:

3372

East Asian (EAS)

AF:

0.130

AC:

559

AN:

4316

South Asian (SAS)

AF:

0.122

AC:

494

AN:

4056

European-Finnish (FIN)

AF:

0.173

AC:

1641

AN:

9474

Middle Eastern (MID)

AF:

0.162

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.175

AC:

11527

AN:

66044

Other (OTH)

AF:

0.127

AC:

261

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

906

1812

2719

3625

4531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.129

Hom.:

495

Bravo

AF:

0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.3

(source)

DANN

Benign

0.88

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over