rs12184389

Variant names:

• chr10-113080011-T-A
• rs12184389
• NM_001367943.1:c.552+39885T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113080011-T-A
• chr10-113080011-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.552+39885T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,634 control chromosomes in the GnomAD database, including 3,421 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 0.19 (3421 hom., cov: 30)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.552+39885T>A		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.552+39885T>A		intron_variant	Intron 5 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28942 AN: 151516 Hom.: 3411 Cov.: 30

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.191 AC: 28977 AN: 151634 Hom.: 3421 Cov.: 30 AF XY: 0.185 AC XY: 13720 AN XY: 74074

African (AFR) AF: 0.326 AC: 13450 AN: 41238

American (AMR) AF: 0.159 AC: 2422 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3470

East Asian (EAS) AF: 0.00195 AC: 10 AN: 5130

South Asian (SAS) AF: 0.0777 AC: 372 AN: 4788

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10282 AN: 67938

Other (OTH) AF: 0.207 AC: 436 AN: 2104

Alfa AF: 0.162 Hom.: 304

Bravo AF: 0.201

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.34
PhyloP100		-0.11
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: rs12184389; hg19: chr10-114839770;