10-113105730-C-T

Position:

• chr10-113105730-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.553-35454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,052 control chromosomes in the GnomAD database, including 48,190 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 0.79 (48190 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.553-35454C>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.553-35454C>T		intron_variant		1	NM_001367943.1	ENSP00000348274

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120640 AN: 151934 Hom.: 48134 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.794 AC: 120756 AN: 152052 Hom.: 48190 Cov.: 32 AF XY: 0.798 AC XY: 59304 AN XY: 74320

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.782

Alfa AF: 0.754 Hom.: 61870

Bravo AF: 0.796

Asia WGS AF: 0.853 AC: 2968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.83

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: rs10749128; hg19: chr10-114865489;