Variant rs5742913 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003202.5(TCF7):c.400C>A(p.Pro134Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,646 control chromosomes in the GnomAD database, including 8,276 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 538 hom., cov: 33)

Exomes 𝑓: 0.099 ( 7738 hom. )

Consequence

TCF7
NM_003202.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

TCF7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015558004).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7	NM_003202.5 linkuse as main transcript	c.400C>A	p.Pro134Thr	missense_variant	3/10	ENST00000342854.10	NP_003193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7	ENST00000342854.10 linkuse as main transcript	c.400C>A	p.Pro134Thr	missense_variant	3/10	1	NM_003202.5	ENSP00000340347	P1	P36402-5

Frequencies

GnomAD3 genomes

AF:

0.0761

AC:

11576

AN:

152192

Hom.:

538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0907

GnomAD3 exomes

AF:

0.0839

AC:

20937

AN:

249658

Hom.:

1103

AF XY:

0.0831

AC XY:

11248

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.0955

Gnomad ASJ exome

AF:

0.136

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.0970

GnomAD4 exome

AF:

0.0990

AC:

144692

AN:

1461336

Hom.:

7738

Cov.:

AF XY:

0.0972

AC XY:

70677

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.0962

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.0275

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.0934

GnomAD4 genome

AF:

0.0760

AC:

11578

AN:

152310

Hom.:

538

Cov.:

AF XY:

0.0749

AC XY:

5578

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0898

Alfa

AF:

0.0907

Hom.:

933

Bravo

AF:

0.0745

TwinsUK

AF:

0.101

AC:

373

ALSPAC

AF:

0.104

AC:

402

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.109

AC:

941

ExAC

AF:

0.0816

AC:

9900

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.106

EpiControl

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.14

CADD

Benign

0.12

DANN

Benign

0.81

DEOGEN2

Benign

0.31

.;T;T;.;.;T;.;.;.;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.37

T;T;T;T;T;T;T;.;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.11

MutationAssessor

Benign

0.69

N;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.62

N;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.17

T;T;D;D;D;D;D;T;D;T

Sift4G

Benign

0.25

T;T;D;D;D;D;D;D;D;D

Polyphen

0.0

B;B;.;.;.;.;.;.;.;.

Vest4

0.096

MPC

0.28

ClinPred

0.020

GERP RS

-10

gMVP

0.40

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