rs3814573

Variant names:

• chr10-113138334-T-C
• rs3814573
• NM_001367943.1:c.553-2850T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-113138334-T-C
• chr10-113138334-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.553-2850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 148,286 control chromosomes in the GnomAD database, including 37,361 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 0.70 (37361 hom., cov: 24)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80
• Publications: 25 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 (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.553-2850T>C		intron_variant	Intron 5 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.553-2850T>C		intron_variant	Intron 5 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.703 AC: 104134 AN: 148180 Hom.: 37322 Cov.: 24

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.703 AC: 104223 AN: 148286 Hom.: 37361 Cov.: 24 AF XY: 0.703 AC XY: 50568 AN XY: 71954

African (AFR) AF: 0.874 AC: 35685 AN: 40812

American (AMR) AF: 0.727 AC: 10699 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2223 AN: 3444

East Asian (EAS) AF: 0.328 AC: 1453 AN: 4436

South Asian (SAS) AF: 0.575 AC: 2596 AN: 4518

European-Finnish (FIN) AF: 0.665 AC: 6528 AN: 9810

Middle Eastern (MID) AF: 0.703 AC: 194 AN: 276

European-Non Finnish (NFE) AF: 0.635 AC: 42776 AN: 67316

Other (OTH) AF: 0.692 AC: 1424 AN: 2058

Alfa AF: 0.654 Hom.: 104822

Bravo AF: 0.705

Asia WGS AF: 0.472 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.50
PhyloP100		-3.8
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: rs3814573; hg19: chr10-114898093;