Variant rs11547160 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031283.3(TCF7L1):c.1597G>A(p.Gly533Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 1,613,332 control chromosomes in the GnomAD database, including 2,955 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.038 ( 172 hom., cov: 31)

Exomes 𝑓: 0.058 ( 2783 hom. )

Consequence

TCF7L1
NM_031283.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

TCF7L1 (HGNC:11640): (transcription factor 7 like 1) This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. [provided by RefSeq, Nov 2010]

TCF7L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018329918).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3 link	c.1597G>A	p.Gly533Arg	missense_variant	12/12	ENST00000282111.4	NP_112573.1	Q9HCS4
TCF7L1	XM_006712109.3 link	c.1600G>A	p.Gly534Arg	missense_variant	12/12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4 link	c.1597G>A	p.Gly533Arg	missense_variant	12/12	1	NM_031283.3	ENSP00000282111.3		Q9HCS4

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5819

AN:

152040

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0497

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0360

GnomAD3 exomes

AF:

0.0417

AC:

10377

AN:

248750

Hom.:

296

AF XY:

0.0438

AC XY:

5913

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.0600

Gnomad OTH exome

AF:

0.0430

GnomAD4 exome

AF:

0.0580

AC:

84813

AN:

1461174

Hom.:

2783

Cov.:

AF XY:

0.0582

AC XY:

42338

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00944

Gnomad4 AMR exome

AF:

0.0278

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0577

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.0662

Gnomad4 OTH exome

AF:

0.0499

GnomAD4 genome

AF:

0.0382

AC:

5816

AN:

152158

Hom.:

172

Cov.:

AF XY:

0.0366

AC XY:

2721

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0496

Gnomad4 FIN

AF:

0.0164

Gnomad4 NFE

AF:

0.0619

Gnomad4 OTH

AF:

0.0356

Alfa

AF:

0.0541

Hom.:

671

Bravo

AF:

0.0373

TwinsUK

AF:

0.0685

AC:

254

ALSPAC

AF:

0.0646

AC:

249

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.0621

AC:

534

ExAC

AF:

0.0420

AC:

5094

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0577

EpiControl

AF:

0.0583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0018

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.77

REVEL

Benign

0.21

Sift

Uncertain

0.010

Sift4G

Benign

0.53

Polyphen

0.12

Vest4

0.049

MutPred

0.11

Gain of MoRF binding (P = 0.0114);

MPC

0.34

ClinPred

0.0041

GERP RS

0.084

Varity_R

0.079

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over