NM_031283.3:c.478T>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031283.3(TCF7L1):c.478T>A(p.Ser160Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,112 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 26 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 19 hom. )

Consequence

TCF7L1
NM_031283.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0630

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007574886).

BP6

Variant 2-85283531-T-A is Benign according to our data. Variant chr2-85283531-T-A is described in ClinVar as [Benign]. Clinvar id is 784988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0099 (1507/152236) while in subpopulation AFR AF= 0.0338 (1402/41524). AF 95% confidence interval is 0.0323. There are 26 homozygotes in gnomad4. There are 730 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1507 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3 link	c.478T>A	p.Ser160Thr	missense_variant	Exon 4 of 12	ENST00000282111.4	NP_112573.1	Q9HCS4
TCF7L1	XM_006712109.3 link	c.478T>A	p.Ser160Thr	missense_variant	Exon 4 of 12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4 link	c.478T>A	p.Ser160Thr	missense_variant	Exon 4 of 12	1	NM_031283.3	ENSP00000282111.3		Q9HCS4
TCF7L1	ENST00000442813.1 link	c.28T>A	p.Ser10Thr	missense_variant	Exon 5 of 6	5		ENSP00000388984.1		C9JPE3

Frequencies

GnomAD3 genomes

AF:

0.00987

AC:

1502

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00332

AC:

834

AN:

251480

Hom.:

AF XY:

0.00283

AC XY:

385

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00609

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00148

AC:

2165

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1049

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00322

Gnomad4 SAS exome

AF:

0.00414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.00311

GnomAD4 genome

AF:

0.00990

AC:

1507

AN:

152236

Hom.:

Cov.:

AF XY:

0.00981

AC XY:

730

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.0106

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00395

AC:

480

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0076

T;T

MetaSVM

Uncertain

0.053

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.81

N;D

REVEL

Uncertain

0.36

Sift

Benign

0.034

D;T

Sift4G

Benign

0.19

T;T

Polyphen

0.39

B;.

Vest4

0.31

MVP

0.71

MPC

0.23

ClinPred

0.015

GERP RS

3.1

Varity_R

0.088

gMVP

0.22

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