rs115942112

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

combined pituitary hormone deficiencies, genetic form
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

TCF7L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1507 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031283.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	NM_031283.3	MANE Select	c.478T>A	p.Ser160Thr	missense	Exon 4 of 12	NP_112573.1	Q9HCS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.478T>A	p.Ser160Thr	missense	Exon 4 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.478T>A	p.Ser160Thr	missense	Exon 4 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.478T>A	p.Ser160Thr	missense	Exon 4 of 12	ENSP00000538161.1

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

GnomAD2 exomes

AF:

0.00332

AC:

834

AN:

251480

AF XY:

0.00283

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 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

African (AFR)

AF:

0.0352

AC:

1177

AN:

33480

American (AMR)

AF:

0.00168

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000497

AC:

AN:

26136

East Asian (EAS)

AF:

0.00322

AC:

128

AN:

39700

South Asian (SAS)

AF:

0.00414

AC:

357

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000187

AC:

208

AN:

1111998

Other (OTH)

AF:

0.00311

AC:

188

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

132

263

395

526

658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00990

AC:

1507

AN:

152236

Hom.:

Cov.:

AF XY:

0.00981

AC XY:

730

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0338

AC:

1402

AN:

41524

American (AMR)

AF:

0.00320

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00347

AC:

AN:

5180

South Asian (SAS)

AF:

0.00332

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68020

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

146

218

291

364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00193

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.15

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0076

MetaSVM

Uncertain

0.053

MutationAssessor

Benign

1.5

PhyloP100

0.063

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.81

REVEL

Uncertain

0.36

Sift

Benign

0.034

Sift4G

Benign

0.19

Polyphen

0.39

Vest4

0.31

MVP

0.71

MPC

0.23

ClinPred

0.015

GERP RS

3.1

Varity_R

0.088

gMVP

0.22

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over