rs11196236

Variant names:

• chr10-113127963-T-C
• rs11196236
• NM_001367943.1:c.553-13221T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001367943.1(TCF7L2):​c.553-13221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,108 control chromosomes in the GnomAD database, including 2,460 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 0.16 (2460 hom., cov: 29)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 12 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, STRONG Submitted by: G2P, PanelApp Australia
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367943.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	NM_001367943.1	MANE Select	c.553-13221T>C		intron	N/A	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.553-13221T>C		intron	N/A	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.484-13221T>C		intron	N/A	NP_110383.2	Q9NQB0-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	ENST00000355995.9	TSL:1 MANE Select	c.553-13221T>C		intron	N/A	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.553-13221T>C		intron	N/A	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000369397.8	TSL:1	c.484-13221T>C		intron	N/A	ENSP00000358404.4	Q9NQB0-8

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24706 AN: 150998 Hom.: 2464 Cov.: 29

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.314

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.163 AC: 24701 AN: 151108 Hom.: 2460 Cov.: 29 AF XY: 0.159 AC XY: 11730 AN XY: 73778

African (AFR) AF: 0.0903 AC: 3722 AN: 41204

American (AMR) AF: 0.206 AC: 3118 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3466

East Asian (EAS) AF: 0.00215 AC: 11 AN: 5120

South Asian (SAS) AF: 0.125 AC: 593 AN: 4740

European-Finnish (FIN) AF: 0.107 AC: 1106 AN: 10366

Middle Eastern (MID) AF: 0.316 AC: 91 AN: 288

European-Non Finnish (NFE) AF: 0.215 AC: 14561 AN: 67808

Other (OTH) AF: 0.209 AC: 434 AN: 2080

Alfa AF: 0.207 Hom.: 6368

Bravo AF: 0.167

Asia WGS AF: 0.0690 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11196236; hg19: chr10-114887722;