chr10-113034064-T-A

Variant names:

• chr10-113034064-T-A
• rs7900150
• NM_001367943.1:c.451-5961T>A

Variant summary

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

The NM_001367943.1(TCF7L2):​c.451-5961T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,084 control chromosomes in the GnomAD database, including 24,314 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 0.53 (24314 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• 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 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.451-5961T>A		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.451-5961T>A		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80841 AN: 151966 Hom.: 24254 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.532 AC: 80946 AN: 152084 Hom.: 24314 Cov.: 32 AF XY: 0.522 AC XY: 38822 AN XY: 74356

African (AFR) AF: 0.806 AC: 33437 AN: 41498

American (AMR) AF: 0.403 AC: 6163 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1482 AN: 3466

East Asian (EAS) AF: 0.0334 AC: 173 AN: 5180

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4521 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31579 AN: 67960

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.511 Hom.: 2644

Bravo AF: 0.538

Asia WGS AF: 0.232 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.9
DANN	Benign	0.79
PhyloP100		0.80
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: rs7900150; hg19: chr10-114793823;