Variant 2-85283654-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031283.3(TCF7L1):c.525+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,494,956 control chromosomes in the GnomAD database, including 190,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24269 hom., cov: 32)

Exomes 𝑓: 0.50 ( 166251 hom. )

Consequence

TCF7L1
NM_031283.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

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 (BayesDel_noAF=-0.88).

BP6

Variant 2-85283654-A-G is Benign according to our data. Variant chr2-85283654-A-G is described in ClinVar as [Benign]. Clinvar id is 1277108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3 linkuse as main transcript	c.525+76A>G		intron_variant		ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3 linkuse as main transcript	c.525+76A>G		intron_variant			XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4 linkuse as main transcript	c.525+76A>G		intron_variant		1	NM_031283.3	ENSP00000282111	P1
TCF7L1	ENST00000442813.1 linkuse as main transcript	c.75+76A>G		intron_variant		5		ENSP00000388984

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84126

AN:

151954

Hom.:

24230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.739

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.541

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.531

GnomAD4 exome

AF:

0.496

AC:

665812

AN:

1342884

Hom.:

166251

AF XY:

0.496

AC XY:

334595

AN XY:

674042

show subpopulations

Gnomad4 AFR exome

AF:

0.748

Gnomad4 AMR exome

AF:

0.520

Gnomad4 ASJ exome

AF:

0.504

Gnomad4 EAS exome

AF:

0.455

Gnomad4 SAS exome

AF:

0.546

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.510

GnomAD4 genome

AF:

0.554

AC:

84220

AN:

152072

Hom.:

24269

Cov.:

AF XY:

0.547

AC XY:

40670

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.739

Gnomad4 AMR

AF:

0.517

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.416

Gnomad4 NFE

AF:

0.484

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.511

Hom.:

4695

Bravo

AF:

0.570

Asia WGS

AF:

0.532

AC:

1849

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.014

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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