10-113126112-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367943.1(TCF7L2):c.553-15072G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 124,948 control chromosomes in the GnomAD database, including 28,632 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 0.71 (28632 hom., cov: 25)
  • Failed GnomAD Quality Control
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.553-15072G>T		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.553-15072G>T		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 89224 AN: 124846 Hom.: 28599 Cov.: 25

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.715

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.715 AC: 89304 AN: 124948 Hom.: 28632 Cov.: 25 AF XY: 0.717 AC XY: 43756 AN XY: 61038

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.712

Alfa AF: 0.328 Hom.: 69

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	13
Dann	Benign	0.85

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

Other links and lift over

dbSNP: rs290494; hg19: chr10-114885871;