rs12573128

chr10-112971038-A-Gchr10-112971038-A-T

Variant summary

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

The NM_001367943.1(TCF7L2):c.450+6414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,064 control chromosomes in the GnomAD database, including 10,222 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 0.30 (10222 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.450+6414A>G		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+6414A>G		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45304 AN: 151946 Hom.: 10174 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.299 AC: 45403 AN: 152064 Hom.: 10222 Cov.: 32 AF XY: 0.300 AC XY: 22268 AN XY: 74334

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.282

Alfa AF: 0.176 Hom.: 2439

Bravo AF: 0.323

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.7
Dann	Benign	0.59

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: rs12573128; hg19: chr10-114730797;