10-112950449-GTTTT-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001367943.1(TCF7L2):​c.-297_-294delTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 195,186 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 17)
Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00172 (207/120642) while in subpopulation AMR AF= 0.0177 (203/11440). AF 95% confidence interval is 0.0157. There are 2 homozygotes in gnomad4. There are 140 alleles in male gnomad4 subpopulation. Median coverage is 17. This position pass quality control queck.
BS2
High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF7L2NM_001367943.1 linkc.-297_-294delTTTT 5_prime_UTR_variant Exon 1 of 15 ENST00000355995.9 NP_001354872.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCF7L2ENST00000355995 linkc.-297_-294delTTTT 5_prime_UTR_variant Exon 1 of 15 1 NM_001367943.1 ENSP00000348274.4 Q9NQB0-1

Frequencies

GnomAD3 genomes
AF:
0.00172
AC:
207
AN:
120632
Hom.:
2
Cov.:
17
show subpopulations
Gnomad AFR
AF:
0.0000309
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0178
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000171
Gnomad OTH
AF:
0.00125
GnomAD4 exome
AF:
0.000322
AC:
24
AN:
74544
Hom.:
0
AF XY:
0.000215
AC XY:
8
AN XY:
37228
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.00934
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000190
GnomAD4 genome
AF:
0.00172
AC:
207
AN:
120642
Hom.:
2
Cov.:
17
AF XY:
0.00246
AC XY:
140
AN XY:
56922
show subpopulations
Gnomad4 AFR
AF:
0.0000309
Gnomad4 AMR
AF:
0.0177
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000171
Gnomad4 OTH
AF:
0.00125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs74804400; hg19: chr10-114710208; API