rs11196175

Variant names:

• chr10-112976855-T-C
• rs11196175
• NM_001367943.1:c.450+12231T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-112976855-T-C
• chr10-112976855-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367943.1(TCF7L2):​c.450+12231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,196 control chromosomes in the GnomAD database, including 3,841 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 0.20 (3841 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 16 publications found

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]

TCF7L2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital glaucoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+12231T>C		intron_variant	Intron 4 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+12231T>C		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29862 AN: 152078 Hom.: 3842 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.196 AC: 29857 AN: 152196 Hom.: 3841 Cov.: 32 AF XY: 0.192 AC XY: 14283 AN XY: 74404

African (AFR) AF: 0.0510 AC: 2121 AN: 41550

American (AMR) AF: 0.205 AC: 3129 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1986 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19649 AN: 68002

Other (OTH) AF: 0.241 AC: 507 AN: 2104

Alfa AF: 0.225 Hom.: 1989

Bravo AF: 0.188

Asia WGS AF: 0.0930 AC: 327 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	4.7
DANN	Benign	0.28
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11196175; hg19: chr10-114736614;