rs11196229

chr10-113106413-G-A

Variant summary

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

The NM_001367943.1(TCF7L2):c.553-34771G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,108 control chromosomes in the GnomAD database, including 3,324 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 0.19 (3324 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.553-34771G>A		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.553-34771G>A		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28491 AN: 151990 Hom.: 3316 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.187 AC: 28504 AN: 152108 Hom.: 3324 Cov.: 32 AF XY: 0.191 AC XY: 14208 AN XY: 74362

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.0987

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.159

Alfa AF: 0.216 Hom.: 1889

Bravo AF: 0.180

Asia WGS AF: 0.0930 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.4
Dann	Benign	0.56

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: rs11196229; hg19: chr10-114866172;