dbSNP rs17881268: TGFBR3:c.62-51C>T (chr1-91797522-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003243.5(TGFBR3):c.62-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,607,956 control chromosomes in the GnomAD database, including 688 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 0.018 ( 36 hom., cov: 33)

Exomes 𝑓: 0.027 ( 652 hom. )

Consequence

TGFBR3
NM_003243.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

Publications

5 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=-0.82).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0176 (2675/152342) while in subpopulation NFE AF = 0.0298 (2025/68038). AF 95% confidence interval is 0.0287. There are 36 homozygotes in GnomAd4. There are 1222 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2675 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5 link	c.62-51C>T		intron_variant	Intron 2 of 16	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.62-51C>T		intron_variant	Intron 2 of 16	1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2677

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00526

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0183

AC:

4523

AN:

246576

AF XY:

0.0192

show subpopulations

Gnomad AFR exome

AF:

0.00487

Gnomad AMR exome

AF:

0.00677

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0179

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0271

AC:

39406

AN:

1455614

Hom.:

652

Cov.:

AF XY:

0.0267

AC XY:

19323

AN XY:

724560

show subpopulations

African (AFR)

AF:

0.00513

AC:

171

AN:

33336

American (AMR)

AF:

0.00687

AC:

307

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00797

AC:

208

AN:

26082

East Asian (EAS)

AF:

0.000126

AC:

AN:

39670

South Asian (SAS)

AF:

0.0188

AC:

1616

AN:

85876

European-Finnish (FIN)

AF:

0.0174

AC:

928

AN:

53378

Middle Eastern (MID)

AF:

0.00608

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0314

AC:

34805

AN:

1106706

Other (OTH)

AF:

0.0221

AC:

1331

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1980

3960

5939

7919

9899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1282

2564

3846

5128

6410

<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:

0.0176

AC:

2675

AN:

152342

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1222

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00527

AC:

219

AN:

41586

American (AMR)

AF:

0.00699

AC:

107

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0191

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0173

AC:

184

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0298

AC:

2025

AN:

68038

Other (OTH)

AF:

0.0118

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0243

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.91

(source)

DANN

Benign

0.44

PhyloP100

0.026

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over