rs7924080

chr10-113027253-T-Cchr10-113027253-T-G

Variant summary

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

The NM_001367943.1(TCF7L2):c.451-12772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,002 control chromosomes in the GnomAD database, including 24,662 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 0.54 (24662 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.451-12772T>C		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.451-12772T>C		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81602 AN: 151884 Hom.: 24603 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.538 AC: 81705 AN: 152002 Hom.: 24662 Cov.: 32 AF XY: 0.526 AC XY: 39124 AN XY: 74332

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.538

Alfa AF: 0.422 Hom.: 3585

Bravo AF: 0.543

Asia WGS AF: 0.236 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.40
Dann	Benign	0.49

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: rs7924080; hg19: chr10-114787012;