chr10-112950260-G-T

Position:

• chr10-112950260-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.-497G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0304 in 186,790 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (291 hom., cov: 26)
  • Exomes 𝑓: 0.011 (18 hom.)
• Consequence: TCF7L2 NM_001367943.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.00

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=-0.23).
• BP6: Variant 10-112950260-G-T is Benign according to our data. Variant chr10-112950260-G-T is described in ClinVar as [Benign]. Clinvar id is 1222749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.-497G>T		5_prime_UTR_variant	1/15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995	c.-497G>T		5_prime_UTR_variant	1/15	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5181 AN: 142276 Hom.: 288 Cov.: 26

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00775

Gnomad NFE AF: 0.000584

Gnomad OTH AF: 0.0289

GnomAD4 exome AF: 0.0107 AC: 477 AN: 44440 Hom.: 18 Cov.: 0 AF XY: 0.0104 AC XY: 221 AN XY: 21226

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.0450

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000747

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0366 AC: 5204 AN: 142350 Hom.: 291 Cov.: 26 AF XY: 0.0361 AC XY: 2466 AN XY: 68338

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000907

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000584

Gnomad4 OTH AF: 0.0287

Alfa AF: 0.0170 Hom.: 26

Bravo AF: 0.0407

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77172590; hg19: chr10-114710019;