Genetic Variant TGFBR3:c.1566+55C>A (chr1-91719257-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003243.5(TGFBR3):c.1566+55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,611,200 control chromosomes in the GnomAD database, including 54,374 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 0.28 ( 6689 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47685 hom. )

Consequence

TGFBR3
NM_003243.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

12 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:

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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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003243.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGFBR3	NM_003243.5	MANE Select	c.1566+55C>A	intron	N/A	NP_003234.2	Q03167-1
TGFBR3	NM_001195683.2		c.1563+55C>A	intron	N/A	NP_001182612.1	A0A0A8KWK3
TGFBR3	NM_001195684.1		c.1563+55C>A	intron	N/A	NP_001182613.1	A0A0A8KWK3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.1566+55C>A	intron	N/A	ENSP00000212355.4	Q03167-1
TGFBR3	ENST00000525962.5	TSL:1	c.1566+55C>A	intron	N/A	ENSP00000436127.1	Q03167-1
TGFBR3	ENST00000370399.6	TSL:1	c.1563+55C>A	intron	N/A	ENSP00000359426.2	Q03167-2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42861

AN:

151940

Hom.:

6676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0735

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.249

AC:

363907

AN:

1459142

Hom.:

47685

AF XY:

0.246

AC XY:

178612

AN XY:

726016

show subpopulations

African (AFR)

AF:

0.405

AC:

13542

AN:

33432

American (AMR)

AF:

0.130

AC:

5816

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4875

AN:

26112

East Asian (EAS)

AF:

0.0740

AC:

2936

AN:

39652

South Asian (SAS)

AF:

0.143

AC:

12281

AN:

86144

European-Finnish (FIN)

AF:

0.278

AC:

14820

AN:

53356

Middle Eastern (MID)

AF:

0.231

AC:

1330

AN:

5760

European-Non Finnish (NFE)

AF:

0.265

AC:

293819

AN:

1109666

Other (OTH)

AF:

0.240

AC:

14488

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14916

29833

44749

59666

74582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9752

19504

29256

39008

48760

<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:

0.282

AC:

42909

AN:

152058

Hom.:

6689

Cov.:

AF XY:

0.277

AC XY:

20597

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.397

AC:

16446

AN:

41442

American (AMR)

AF:

0.190

AC:

2898

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

589

AN:

3460

East Asian (EAS)

AF:

0.0735

AC:

380

AN:

5172

South Asian (SAS)

AF:

0.130

AC:

625

AN:

4822

European-Finnish (FIN)

AF:

0.278

AC:

2945

AN:

10588

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18054

AN:

67980

Other (OTH)

AF:

0.275

AC:

582

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1541

3082

4623

6164

7705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.259

Hom.:

8482

Bravo

AF:

0.284

Asia WGS

AF:

0.128

AC:

446

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.045

(source)

DANN

Benign

0.40

PhyloP100

-1.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over