rs12184389

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000355995.9(TCF7L2):​c.552+39885T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,634 control chromosomes in the GnomAD database, including 3,421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3421 hom., cov: 30)

Consequence

TCF7L2
ENST00000355995.9 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.107
Variant links:
Genes affected
TCF7L2 (HGNC:11641): (transcription factor 7 like 2) This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TCF7L2NM_001367943.1 linkuse as main transcriptc.552+39885T>A intron_variant ENST00000355995.9 NP_001354872.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TCF7L2ENST00000355995.9 linkuse as main transcriptc.552+39885T>A intron_variant 1 NM_001367943.1 ENSP00000348274 Q9NQB0-1

Frequencies

GnomAD3 genomes
AF:
0.191
AC:
28942
AN:
151516
Hom.:
3411
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.326
Gnomad AMI
AF:
0.201
Gnomad AMR
AF:
0.160
Gnomad ASJ
AF:
0.177
Gnomad EAS
AF:
0.00194
Gnomad SAS
AF:
0.0766
Gnomad FIN
AF:
0.107
Gnomad MID
AF:
0.250
Gnomad NFE
AF:
0.151
Gnomad OTH
AF:
0.210
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.191
AC:
28977
AN:
151634
Hom.:
3421
Cov.:
30
AF XY:
0.185
AC XY:
13720
AN XY:
74074
show subpopulations
Gnomad4 AFR
AF:
0.326
Gnomad4 AMR
AF:
0.159
Gnomad4 ASJ
AF:
0.177
Gnomad4 EAS
AF:
0.00195
Gnomad4 SAS
AF:
0.0777
Gnomad4 FIN
AF:
0.107
Gnomad4 NFE
AF:
0.151
Gnomad4 OTH
AF:
0.207
Alfa
AF:
0.162
Hom.:
304
Bravo
AF:
0.201
Asia WGS
AF:
0.0640
AC:
225
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.79
DANN
Benign
0.34

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.

Other links and lift over

dbSNP: rs12184389; hg19: chr10-114839770; API