NM_001367943.1:c.552+7162G>C

Variant names:

• chr10-113047288-G-C
• rs11196205
• NM_001367943.1:c.552+7162G>C

Variant summary

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

The NM_001367943.1(TCF7L2):​c.552+7162G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,016 control chromosomes in the GnomAD database, including 23,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.53 (23737 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.932
• Publications: 111 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	NM_001367943.1	MANE Select	c.552+7162G>C		intron	N/A	NP_001354872.1
	TCF7L2	NM_001146274.2		c.552+7162G>C		intron	N/A	NP_001139746.1
	TCF7L2	NM_030756.5		c.483+7162G>C		intron	N/A	NP_110383.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	ENST00000355995.9	TSL:1 MANE Select	c.552+7162G>C		intron	N/A	ENSP00000348274.4
	TCF7L2	ENST00000627217.3	TSL:1	c.552+7162G>C		intron	N/A	ENSP00000486891.1
	TCF7L2	ENST00000369397.8	TSL:1	c.483+7162G>C		intron	N/A	ENSP00000358404.4

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80397 AN: 151898 Hom.: 23689 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.529 AC: 80486 AN: 152016 Hom.: 23737 Cov.: 32 AF XY: 0.519 AC XY: 38577 AN XY: 74292

African (AFR) AF: 0.776 AC: 32180 AN: 41464

American (AMR) AF: 0.409 AC: 6253 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5178

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4536 AN: 10538

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32122 AN: 67976

Other (OTH) AF: 0.532 AC: 1120 AN: 2106

Alfa AF: 0.336 Hom.: 773

Bravo AF: 0.533

Asia WGS AF: 0.234 AC: 818 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to Other:1

Jan 01, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.056
DANN	Benign	0.27
PhyloP100		-0.93
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: rs11196205; hg19: chr10-114807047;