10-112951110-ACC-ACCC

Variant names:

• chr10-112951110-A-AC
• rs72101402
• NM_001367943.1:c.190-89dupC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001367943.1(TCF7L2):​c.190-89dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,047,216 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

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]

ENSG00000233547 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.190-89dupC		intron_variant	Intron 1 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.190-97_190-96insC		intron_variant	Intron 1 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.000345 AC: 49 AN: 141950 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000208

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000631

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000108

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.000226 AC: 205 AN: 905172 Hom.: 0 Cov.: 5 AF XY: 0.000219 AC XY: 100 AN XY: 457274

Gnomad4 AFR exome AF: 0.000779

Gnomad4 AMR exome AF: 0.000160

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000354

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.0000224

Gnomad4 NFE exome AF: 0.000225

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.000345 AC: 49 AN: 142044 Hom.: 0 Cov.: 21 AF XY: 0.000290 AC XY: 20 AN XY: 69018

Gnomad4 AFR AF: 0.000877

Gnomad4 AMR AF: 0.000207

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000634

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000108

Gnomad4 OTH AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs72101402; hg19: chr10-114710869;