10-113087964-A-G

Variant names:

• chr10-113087964-A-G
• rs3814572
• NM_001367943.1:c.552+47838A>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.552+47838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,146 control chromosomes in the GnomAD database, including 1,154 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 0.11 (1154 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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+47838A>G		intron	N/A	NP_001354872.1
	TCF7L2	NM_001146274.2		c.552+47838A>G		intron	N/A	NP_001139746.1
	TCF7L2	NM_030756.5		c.483+47838A>G		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+47838A>G		intron	N/A	ENSP00000348274.4
	TCF7L2	ENST00000627217.3	TSL:1	c.552+47838A>G		intron	N/A	ENSP00000486891.1
	TCF7L2	ENST00000369397.8	TSL:1	c.483+47838A>G		intron	N/A	ENSP00000358404.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16725 AN: 152028 Hom.: 1155 Cov.: 32

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.110 AC: 16724 AN: 152146 Hom.: 1154 Cov.: 32 AF XY: 0.109 AC XY: 8116 AN XY: 74354

African (AFR) AF: 0.0289 AC: 1199 AN: 41522

American (AMR) AF: 0.0982 AC: 1500 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3470

East Asian (EAS) AF: 0.0738 AC: 383 AN: 5188

South Asian (SAS) AF: 0.156 AC: 749 AN: 4812

European-Finnish (FIN) AF: 0.126 AC: 1331 AN: 10580

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10725 AN: 67998

Other (OTH) AF: 0.124 AC: 260 AN: 2102

Alfa AF: 0.136 Hom.: 2053

Bravo AF: 0.103

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.71
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3814572; hg19: chr10-114847723;