rs12243326

Positions:

• chr10-113029056-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367943.1(TCF7L2):​c.451-10969T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,100 control chromosomes in the GnomAD database, including 5,816 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 0.27 (5816 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.451-10969T>C		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.451-10969T>C		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40635 AN: 151982 Hom.: 5805 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.267 AC: 40663 AN: 152100 Hom.: 5816 Cov.: 32 AF XY: 0.259 AC XY: 19281 AN XY: 74352

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.314

Alfa AF: 0.273 Hom.: 11989

Bravo AF: 0.275

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12243326; hg19: chr10-114788815;