rs11196236

Positions:

• chr10-113127963-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000355995.9(TCF7L2):​c.553-13221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,108 control chromosomes in the GnomAD database, including 2,460 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 0.16 (2460 hom., cov: 29)
• Consequence: TCF7L2 ENST00000355995.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.553-13221T>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.553-13221T>C		intron_variant		1	NM_001367943.1	ENSP00000348274

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24706 AN: 150998 Hom.: 2464 Cov.: 29

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.163 AC: 24701 AN: 151108 Hom.: 2460 Cov.: 29 AF XY: 0.159 AC XY: 11730 AN XY: 73778

Gnomad4 AFR AF: 0.0903

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.00215

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.209

Alfa AF: 0.214 Hom.: 4822

Bravo AF: 0.167

Asia WGS AF: 0.0690 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.81

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: rs11196236; hg19: chr10-114887722;