Variant 16-31474569-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001042454.3(TGFB1I1):c.526G>C(p.Ala176Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,608,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TGFB1I1
NM_001042454.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.969

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03449291).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB1I1	NM_001042454.3 link	c.526G>C	p.Ala176Pro	missense_variant	7/11	ENST00000394863.8	NP_001035919.1	O43294-1
TGFB1I1	NM_001164719.1 link	c.475G>C	p.Ala159Pro	missense_variant	7/11		NP_001158191.1	O43294-2A0A024QZE7
TGFB1I1	NM_015927.5 link	c.475G>C	p.Ala159Pro	missense_variant	7/11		NP_057011.2	O43294-2A0A024QZE7
TGFB1I1	XM_024450412.2 link	c.475G>C	p.Ala159Pro	missense_variant	7/11		XP_024306180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB1I1	ENST00000394863.8 link	c.526G>C	p.Ala176Pro	missense_variant	7/11	1	NM_001042454.3	ENSP00000378332.3		O43294-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

247406

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134012

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1455942

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723340

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.526G>C (p.A176P) alteration is located in exon 7 (coding exon 7) of the TGFB1I1 gene. This alteration results from a G to C substitution at nucleotide position 526, causing the alanine (A) at amino acid position 176 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0066

T;T;.;.;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.73

T;T;T;T;.;.

M_CAP

Benign

0.0069

MetaRNN

Benign

0.034

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

.;L;.;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

0.020

N;N;N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.12

T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

0.023

.;B;.;.;.;.

Vest4

0.20, 0.22, 0.22, 0.22

MutPred

0.29

.;Gain of catalytic residue at P175 (P = 0.0164);.;.;.;.;

MVP

0.38

MPC

0.090

ClinPred

0.050

GERP RS

4.3

Varity_R

0.11

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over