rs11196228

Positions:

• chr10-113104538-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.553-36646T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 152,282 control chromosomes in the GnomAD database, including 380 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 0.057 (380 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.553-36646T>C		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.553-36646T>C		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8665 AN: 152164 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0569 AC: 8660 AN: 152282 Hom.: 380 Cov.: 32 AF XY: 0.0557 AC XY: 4150 AN XY: 74464

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0627

Gnomad4 NFE AF: 0.0829

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0802 Hom.: 167

Bravo AF: 0.0565

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11196228; hg19: chr10-114864297;