rs10749127

Positions:

• chr10-113089594-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367943.1(TCF7L2):​c.552+49468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,589,330 control chromosomes in the GnomAD database, including 67,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6088 hom., cov: 32)
  • Exomes 𝑓: 0.29 (61045 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.719

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-113089594-C-T is Benign according to our data. Variant chr10-113089594-C-T is described in ClinVar as [Benign]. Clinvar id is 1267768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.552+49468C>T		intron_variant		ENST00000355995.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.552+49468C>T		intron_variant		1	NM_001367943.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42680 AN: 151910 Hom.: 6083 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.290 AC: 416240 AN: 1437300 Hom.: 61045 AF XY: 0.291 AC XY: 207705 AN XY: 713038

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.281 AC: 42703 AN: 152030 Hom.: 6088 Cov.: 32 AF XY: 0.282 AC XY: 20953 AN XY: 74308

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.308

Alfa AF: 0.296 Hom.: 8887

Bravo AF: 0.279

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.75

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: rs10749127; hg19: chr10-114849353; COSMIC: COSV60501258;