Genetic Variant TCF7L1:p.Gly17Glu (chr2-85133734-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031283.3(TCF7L1):c.50G>A(p.Gly17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TCF7L1
NM_031283.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Publications

1 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 links:

ENSG00000300535 (HGNC:):

ENSG00000300535 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15033138).

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.50G>A	p.Gly17Glu	missense	Exon 1 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.50G>A	p.Gly17Glu	missense	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
TCF7L1	ENST00000922942.1		c.50G>A	p.Gly17Glu	missense	Exon 1 of 12	ENSP00000593001.1
TCF7L1	ENST00000868102.1		c.50G>A	p.Gly17Glu	missense	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1064012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

503636

African (AFR)

AF:

0.00

AC:

AN:

22166

American (AMR)

AF:

0.00

AC:

AN:

7718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13410

East Asian (EAS)

AF:

0.00

AC:

AN:

25200

South Asian (SAS)

AF:

0.00

AC:

AN:

19386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2820

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

909698

Other (OTH)

AF:

0.00

AC:

AN:

42266

GnomAD4 genome

AF:

0.00000670

AC:

AN:

149276

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41110

American (AMR)

AF:

0.00

AC:

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.000195

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67028

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.092

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.15

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

0.81

PhyloP100

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.14

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Benign

0.26

Polyphen

0.010

Vest4

0.29

MutPred

0.45

Gain of solvent accessibility (P = 0.012)

MVP

0.61

MPC

1.5

ClinPred

0.12

GERP RS

0.28

PromoterAI

0.040

Neutral

(source)

Varity_R

0.33

gMVP

0.51

Mutation Taster

=93/7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over