Variant 2-85133718-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031283.3(TCF7L1):c.34G>A(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,154,898 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 78 hom. )

Consequence

TCF7L1
NM_031283.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.26

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069305897).

BP6

Variant 2-85133718-G-A is Benign according to our data. Variant chr2-85133718-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651091.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1182 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3 linkuse as main transcript	c.34G>A	p.Gly12Ser	missense_variant	1/12	ENST00000282111.4	NP_112573.1	Q9HCS4
TCF7L1	XM_006712109.3 linkuse as main transcript	c.34G>A	p.Gly12Ser	missense_variant	1/12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4 linkuse as main transcript	c.34G>A	p.Gly12Ser	missense_variant	1/12	1	NM_031283.3	ENSP00000282111.3		Q9HCS4

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1182

AN:

148128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00188

Gnomad ASJ

AF:

0.00410

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0484

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00886

Gnomad OTH

AF:

0.00686

GnomAD3 exomes

AF:

0.00936

AC:

AN:

962

Hom.:

AF XY:

0.0106

AC XY:

AN XY:

566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.00787

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00791

AC:

7961

AN:

1006662

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

3675

AN XY:

475128

show subpopulations

Gnomad4 AFR exome

AF:

0.000639

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00369

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00461

Gnomad4 FIN exome

AF:

0.0554

Gnomad4 NFE exome

AF:

0.00753

Gnomad4 OTH exome

AF:

0.00726

GnomAD4 genome

AF:

0.00797

AC:

1182

AN:

148236

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

718

AN XY:

72276

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00188

Gnomad4 ASJ

AF:

0.00410

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.0484

Gnomad4 NFE

AF:

0.00886

Gnomad4 OTH

AF:

0.00678

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00467

ExAC

AF:

0.00190

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TCF7L1: PP2, PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.11

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.0069

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.28

REVEL

Uncertain

0.35

Sift

Benign

0.31

Sift4G

Benign

0.57

Polyphen

0.039

Vest4

0.31

MVP

0.88

MPC

1.2

ClinPred

0.058

GERP RS

1.8

Varity_R

0.080

gMVP

0.25

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