rs11196208

Positions:

• chr10-113051557-T-C

Variant summary

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

The NM_001367943.1(TCF7L2):​c.552+11431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,086 control chromosomes in the GnomAD database, including 23,679 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 0.53 (23679 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.552+11431T>C		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+11431T>C		intron_variant		1	NM_001367943.1	ENSP00000348274

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80323 AN: 151970 Hom.: 23631 Cov.: 33

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.529 AC: 80409 AN: 152086 Hom.: 23679 Cov.: 33 AF XY: 0.519 AC XY: 38550 AN XY: 74336

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.529

Alfa AF: 0.490 Hom.: 6098

Bravo AF: 0.533

Asia WGS AF: 0.234 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.2
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11196208; hg19: chr10-114811316;