10-112950449-GTTTT-GTTT

Variant names:

• chr10-112950449-GT-G
• rs74804400
• NM_001367943.1:c.-294delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001367943.1(TCF7L2):​c.-294delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (25 hom., cov: 17)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: TCF7L2 NM_001367943.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.-294delT		5_prime_UTR_variant	Exon 1 of 15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995	c.-294delT		5_prime_UTR_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1594 AN: 120570 Hom.: 25 Cov.: 17

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00454

Gnomad EAS AF: 0.00170

Gnomad SAS AF: 0.00260

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00400

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.0151

GnomAD4 exome AF: 0.109 AC: 7542 AN: 69076 Hom.: 1 Cov.: 0 AF XY: 0.103 AC XY: 3558 AN XY: 34614

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.0541

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.0132 AC: 1593 AN: 120580 Hom.: 25 Cov.: 17 AF XY: 0.0127 AC XY: 725 AN XY: 56884

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.00560

Gnomad4 ASJ AF: 0.00454

Gnomad4 EAS AF: 0.00170

Gnomad4 SAS AF: 0.00261

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00400

Gnomad4 OTH AF: 0.0150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74804400; hg19: chr10-114710208;