rs12573128

Variant names:

• chr10-112971038-A-G
• rs12573128
• NM_001367943.1:c.450+6414A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-112971038-A-G
• chr10-112971038-A-T

Variant summary

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

The NM_001367943.1(TCF7L2):​c.450+6414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,064 control chromosomes in the GnomAD database, including 10,222 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 0.30 (10222 hom., cov: 32)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 29 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+6414A>G		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.450+6414A>G		intron_variant	Intron 4 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45304 AN: 151946 Hom.: 10174 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.299 AC: 45403 AN: 152064 Hom.: 10222 Cov.: 32 AF XY: 0.300 AC XY: 22268 AN XY: 74334

African (AFR) AF: 0.591 AC: 24502 AN: 41458

American (AMR) AF: 0.228 AC: 3475 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3574 AN: 5144

South Asian (SAS) AF: 0.307 AC: 1477 AN: 4816

European-Finnish (FIN) AF: 0.142 AC: 1502 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9125 AN: 68004

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.183 Hom.: 4398

Bravo AF: 0.323

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		0.47
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: rs12573128; hg19: chr10-114730797;