Genetic Variant TGFB1I1:c.*136C>T (chr16-31477712-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 NM_001042454.3(TGFB1I1):c.*136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,190,998 control chromosomes in the GnomAD database, including 42,745 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 0.25 ( 4758 hom., cov: 31)

Exomes 𝑓: 0.26 ( 37987 hom. )

Consequence

TGFB1I1
NM_001042454.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

13 publications found

Variant links:

Genes affected

TGFB1I1 (HGNC:11767): (transforming growth factor beta 1 induced transcript 1) This gene encodes a coactivator of the androgen receptor, a transcription factor which is activated by androgen and has a key role in male sexual differentiation. The encoded protein is thought to regulate androgen receptor activity and may have a role to play in the treatment of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

TGFB1I1 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGFB1I1	NM_001042454.3 link	c.*136C>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000394863.8	NP_001035919.1	O43294-1
TGFB1I1	NM_001164719.1 link	c.*136C>T	3_prime_UTR_variant	Exon 11 of 11		NP_001158191.1	O43294-2A0A024QZE7
TGFB1I1	NM_015927.5 link	c.*136C>T	3_prime_UTR_variant	Exon 11 of 11		NP_057011.2	O43294-2A0A024QZE7
TGFB1I1	XM_024450412.2 link	c.*136C>T	3_prime_UTR_variant	Exon 11 of 11		XP_024306180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB1I1	ENST00000394863.8 link	c.*136C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001042454.3	ENSP00000378332.3		O43294-1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37239

AN:

151884

Hom.:

4749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.0879

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.265

AC:

275014

AN:

1038996

Hom.:

37987

Cov.:

AF XY:

0.262

AC XY:

134071

AN XY:

511138

show subpopulations

African (AFR)

AF:

0.228

AC:

5386

AN:

23616

American (AMR)

AF:

0.224

AC:

4313

AN:

19214

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

3758

AN:

17256

East Asian (EAS)

AF:

0.114

AC:

3806

AN:

33296

South Asian (SAS)

AF:

0.208

AC:

11715

AN:

56362

European-Finnish (FIN)

AF:

0.263

AC:

7874

AN:

29916

Middle Eastern (MID)

AF:

0.193

AC:

601

AN:

3110

European-Non Finnish (NFE)

AF:

0.279

AC:

226013

AN:

810934

Other (OTH)

AF:

0.255

AC:

11548

AN:

45292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

10060

20120

30181

40241

50301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7250

14500

21750

29000

36250

<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:

0.245

AC:

37269

AN:

152002

Hom.:

4758

Cov.:

AF XY:

0.243

AC XY:

18049

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.231

AC:

9592

AN:

41466

American (AMR)

AF:

0.241

AC:

3692

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

735

AN:

3470

East Asian (EAS)

AF:

0.126

AC:

648

AN:

5154

South Asian (SAS)

AF:

0.192

AC:

924

AN:

4816

European-Finnish (FIN)

AF:

0.261

AC:

2763

AN:

10594

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.270

AC:

18339

AN:

67904

Other (OTH)

AF:

0.206

AC:

434

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1380

2761

4141

5522

6902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.233

Hom.:

1861

Bravo

AF:

0.243

Asia WGS

AF:

0.137

AC:

479

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

(source)

DANN

Benign

0.69

PhyloP100

-1.1

Mutation Taster

=99/1

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