10-112993500-T-C

Variant names:

• chr10-112993500-T-C
• rs61875120
• NM_001367943.1:c.450+28876T>C

Variant summary

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

The NM_001367943.1(TCF7L2):​c.450+28876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,924 control chromosomes in the GnomAD database, including 2,669 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 0.17 (2669 hom., cov: 31)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+28876T>C		intron_variant	Intron 4 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+28876T>C		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25657 AN: 151806 Hom.: 2664 Cov.: 31

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.169 AC: 25673 AN: 151924 Hom.: 2669 Cov.: 31 AF XY: 0.167 AC XY: 12415 AN XY: 74248

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.0188

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.222

Alfa AF: 0.0848 Hom.: 119

Bravo AF: 0.164

Asia WGS AF: 0.104 AC: 364 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.19

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: rs61875120; hg19: chr10-114753259;