dbSNP rs1805115: TGFBR3:n.*2660G>A (chr1-91683582-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.*2660G>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 0.141 in 711,200 control chromosomes in the GnomAD database, including 7,967 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 0.12 ( 1415 hom., cov: 32)

Exomes 𝑓: 0.15 ( 6552 hom. )

Consequence

TGFBR3
ENST00000532540.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440

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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFBR3	NM_003243.5 link	c.*157G>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.*157G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_003243.5	ENSP00000212355.4		Q03167-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18126

AN:

152024

Hom.:

1416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.132

AC:

17763

AN:

134990

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0898

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.173

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.147

AC:

82388

AN:

559058

Hom.:

6552

Cov.:

AF XY:

0.147

AC XY:

44218

AN XY:

301628

show subpopulations

African (AFR)

AF:

0.0318

AC:

499

AN:

15676

American (AMR)

AF:

0.0923

AC:

3147

AN:

34100

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

2772

AN:

19750

East Asian (EAS)

AF:

0.111

AC:

3564

AN:

32054

South Asian (SAS)

AF:

0.105

AC:

6507

AN:

61678

European-Finnish (FIN)

AF:

0.164

AC:

5523

AN:

33680

Middle Eastern (MID)

AF:

0.164

AC:

402

AN:

2452

European-Non Finnish (NFE)

AF:

0.169

AC:

55703

AN:

329086

Other (OTH)

AF:

0.140

AC:

4271

AN:

30582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

3927

7855

11782

15710

19637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.119

AC:

18118

AN:

152142

Hom.:

1415

Cov.:

AF XY:

0.119

AC XY:

8861

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0315

AC:

1309

AN:

41532

American (AMR)

AF:

0.112

AC:

1705

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3472

East Asian (EAS)

AF:

0.104

AC:

539

AN:

5168

South Asian (SAS)

AF:

0.102

AC:

492

AN:

4810

European-Finnish (FIN)

AF:

0.155

AC:

1646

AN:

10594

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11515

AN:

67978

Other (OTH)

AF:

0.112

AC:

236

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

822

1643

2465

3286

4108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<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:

0.149

Hom.:

1230

Bravo

AF:

0.115

Asia WGS

AF:

0.0770

AC:

266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.044

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over