rs10787476

Variant names:

• chr10-113139155-A-C
• rs10787476
• NM_001367943.1:c.553-2029A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-113139155-A-C
• chr10-113139155-A-G

Variant summary

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

The ENST00000355995.9(TCF7L2):​c.553-2029A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,078 control chromosomes in the GnomAD database, including 967 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 0.081 (967 hom., cov: 32)
• Consequence: TCF7L2 ENST00000355995.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355995.9. 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.553-2029A>C		intron	N/A	NP_001354872.1
	TCF7L2	NM_001146274.2		c.553-2029A>C		intron	N/A	NP_001139746.1
	TCF7L2	NM_030756.5		c.484-2029A>C		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.553-2029A>C		intron	N/A	ENSP00000348274.4
	TCF7L2	ENST00000627217.3	TSL:1	c.553-2029A>C		intron	N/A	ENSP00000486891.1
	TCF7L2	ENST00000369397.8	TSL:1	c.484-2029A>C		intron	N/A	ENSP00000358404.4

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12315 AN: 151960 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0916

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

GnomAD4 genome AF: 0.0811 AC: 12329 AN: 152078 Hom.: 967 Cov.: 32 AF XY: 0.0874 AC XY: 6500 AN XY: 74346

African (AFR) AF: 0.0220 AC: 911 AN: 41496

American (AMR) AF: 0.238 AC: 3636 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1165 AN: 5158

South Asian (SAS) AF: 0.217 AC: 1043 AN: 4810

European-Finnish (FIN) AF: 0.0735 AC: 777 AN: 10568

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0630 AC: 4283 AN: 67978

Other (OTH) AF: 0.0944 AC: 199 AN: 2108

Alfa AF: 0.0726 Hom.: 1439

Bravo AF: 0.0906

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.70
PhyloP100		-0.096
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: rs10787476; hg19: chr10-114898914;