10-112998590-C-T

Position:

• chr10-112998590-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.450+33966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,914 control chromosomes in the GnomAD database, including 5,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.27 (5952 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.133

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+33966C>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.450+33966C>T		intron_variant		1	NM_001367943.1	ENSP00000348274

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41569 AN: 151796 Hom.: 5936 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.274 AC: 41622 AN: 151914 Hom.: 5952 Cov.: 32 AF XY: 0.269 AC XY: 19967 AN XY: 74232

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0269

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.317

Alfa AF: 0.287 Hom.: 14744

Bravo AF: 0.277

Asia WGS AF: 0.156 AC: 552 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.59

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: rs7903146; hg19: chr10-114758349;