rs7901695

Variant names:

• chr10-112994329-T-C
• rs7901695
• NM_001367943.1:c.450+29705T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367943.1(TCF7L2):​c.450+29705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,110 control chromosomes in the GnomAD database, including 9,146 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 0.33 (9146 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+29705T>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+29705T>C		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50674 AN: 151992 Hom.: 9107 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.334 AC: 50752 AN: 152110 Hom.: 9146 Cov.: 32 AF XY: 0.327 AC XY: 24269 AN XY: 74330

Gnomad4 AFR AF: 0.456 AC: 0.456023 AN: 0.456023

Gnomad4 AMR AF: 0.297 AC: 0.29657 AN: 0.29657

Gnomad4 ASJ AF: 0.307 AC: 0.307205 AN: 0.307205

Gnomad4 EAS AF: 0.0265 AC: 0.0264683 AN: 0.0264683

Gnomad4 SAS AF: 0.301 AC: 0.30116 AN: 0.30116

Gnomad4 FIN AF: 0.217 AC: 0.216525 AN: 0.216525

Gnomad4 NFE AF: 0.312 AC: 0.312099 AN: 0.312099

Gnomad4 OTH AF: 0.366 AC: 0.365658 AN: 0.365658

Alfa AF: 0.312 Hom.: 33412

Bravo AF: 0.340

Asia WGS AF: 0.167 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs7901695; hg19: chr10-114754088;