10-113065217-C-T

Position:

• chr10-113065217-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.552+25091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,176 control chromosomes in the GnomAD database, including 51,900 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 0.82 (51900 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.552+25091C>T		intron_variant		ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.552+25091C>T		intron_variant		1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124760 AN: 152058 Hom.: 51882 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.820 AC: 124827 AN: 152176 Hom.: 51900 Cov.: 33 AF XY: 0.820 AC XY: 61022 AN XY: 74392

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.836

Alfa AF: 0.882 Hom.: 80013

Bravo AF: 0.806

Asia WGS AF: 0.805 AC: 2799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.65

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: rs7919409; hg19: chr10-114824976;