rs17130192

Positions:

• chr10-113143231-C-T

Variant summary

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

The NM_001367943.1(TCF7L2):​c.686-692C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 152,352 control chromosomes in the GnomAD database, including 358 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 0.060 (358 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.686-692C>T		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.686-692C>T		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9198 AN: 152234 Hom.: 358 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.0659

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0604 AC: 9196 AN: 152352 Hom.: 358 Cov.: 33 AF XY: 0.0603 AC XY: 4495 AN XY: 74500

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.0652

Alfa AF: 0.0754 Hom.: 204

Bravo AF: 0.0575

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.039
DANN	Benign	0.95

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: rs17130192; hg19: chr10-114902990; COSMIC: COSV53350552; COSMIC: COSV53350552;