rs35676242

Positions:

• chr10-112997555-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001367943.1(TCF7L2):​c.450+32931C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 152,284 control chromosomes in the GnomAD database, including 89 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 0.032 (89 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4836/152284) while in subpopulation NFE AF= 0.0422 (2872/68012). AF 95% confidence interval is 0.0409. There are 89 homozygotes in gnomad4. There are 2225 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4836 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.450+32931C>A		intron_variant		ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.450+32931C>A		intron_variant		1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4834 AN: 152164 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0318 AC: 4836 AN: 152284 Hom.: 89 Cov.: 33 AF XY: 0.0299 AC XY: 2225 AN XY: 74466

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0326 Hom.: 27

Bravo AF: 0.0327

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs35676242; hg19: chr10-114757314;