rs35801464

chr10-113000525-C-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+35901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 152,196 control chromosomes in the GnomAD database, including 233 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 0.055 (233 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.450+35901C>T		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+35901C>T		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8350 AN: 152078 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0549 AC: 8352 AN: 152196 Hom.: 233 Cov.: 32 AF XY: 0.0529 AC XY: 3939 AN XY: 74416

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.0531

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0533 Hom.: 45

Bravo AF: 0.0559

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.4
Dann	Benign	0.62

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: rs35801464; hg19: chr10-114760284;