rs17686448

chr10-113150653-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001367943.1(TCF7L2):c.876-345G>C variant causes a intron change. The variant allele was found at a frequency of 0.0222 in 152,182 control chromosomes in the GnomAD database, including 49 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 0.022 (49 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0222 (3379/152182) while in subpopulation SAS AF= 0.0361 (174/4814). AF 95% confidence interval is 0.0318. There are 49 homozygotes in gnomad4. There are 1663 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3376 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.876-345G>C		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.876-345G>C		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3376 AN: 152064 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00743

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0359

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0222 AC: 3379 AN: 152182 Hom.: 49 Cov.: 32 AF XY: 0.0224 AC XY: 1663 AN XY: 74400

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.0300

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0301

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0255 Hom.: 9

Bravo AF: 0.0227

Asia WGS AF: 0.0130 AC: 46 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	18
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17686448; hg19: chr10-114910412;