Genetic Variant TGFBR3:c.2288-99C>A (chr1-91698229-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.2288-99C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,001,802 control chromosomes in the GnomAD database, including 13,932 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 0.15 ( 1814 hom., cov: 32)

Exomes 𝑓: 0.16 ( 12118 hom. )

Consequence

TGFBR3
NM_003243.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0560

Publications

10 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 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
TGFBR3	NM_003243.5	MANE Select	c.2288-99C>A	intron	N/A	NP_003234.2
TGFBR3	NM_001195683.2		c.2285-99C>A	intron	N/A	NP_001182612.1
TGFBR3	NM_001195684.1		c.2285-99C>A	intron	N/A	NP_001182613.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TGFBR3	ENST00000212355.9	TSL:1 MANE Select	c.2288-99C>A	intron	N/A	ENSP00000212355.4
TGFBR3	ENST00000525962.5	TSL:1	c.2288-99C>A	intron	N/A	ENSP00000436127.1
TGFBR3	ENST00000370399.6	TSL:1	c.2285-99C>A	intron	N/A	ENSP00000359426.2

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22241

AN:

152002

Hom.:

1812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0679

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.164

AC:

139032

AN:

849682

Hom.:

12118

AF XY:

0.164

AC XY:

73227

AN XY:

447478

show subpopulations

African (AFR)

AF:

0.0991

AC:

2126

AN:

21452

American (AMR)

AF:

0.0762

AC:

3300

AN:

43300

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

2486

AN:

22292

East Asian (EAS)

AF:

0.0795

AC:

2922

AN:

36742

South Asian (SAS)

AF:

0.130

AC:

9497

AN:

73022

European-Finnish (FIN)

AF:

0.178

AC:

9172

AN:

51602

Middle Eastern (MID)

AF:

0.176

AC:

595

AN:

3390

European-Non Finnish (NFE)

AF:

0.184

AC:

102666

AN:

557662

Other (OTH)

AF:

0.156

AC:

6268

AN:

40220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5756

11512

17268

23024

28780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2140

4280

6420

8560

10700

<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:

0.146

AC:

22257

AN:

152120

Hom.:

1814

Cov.:

AF XY:

0.144

AC XY:

10723

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.101

AC:

4177

AN:

41516

American (AMR)

AF:

0.101

AC:

1541

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

356

AN:

3464

East Asian (EAS)

AF:

0.0679

AC:

351

AN:

5170

South Asian (SAS)

AF:

0.124

AC:

600

AN:

4820

European-Finnish (FIN)

AF:

0.174

AC:

1838

AN:

10562

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12808

AN:

67978

Other (OTH)

AF:

0.143

AC:

302

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

951

1902

2853

3804

4755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.169

Hom.:

1582

Bravo

AF:

0.141

Asia WGS

AF:

0.0910

AC:

315

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.056

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