10-113014168-A-G

Position:

• chr10-113014168-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.451-25857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,974 control chromosomes in the GnomAD database, including 24,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (24623 hom., cov: 33)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 10-113014168-A-G is Benign according to our data. Variant chr10-113014168-A-G is described in ClinVar as [Benign]. Clinvar id is 225819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.451-25857A>G		intron_variant		ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.451-25857A>G		intron_variant		1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81499 AN: 151856 Hom.: 24564 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.537 AC: 81603 AN: 151974 Hom.: 24623 Cov.: 33 AF XY: 0.526 AC XY: 39050 AN XY: 74294

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.536

Alfa AF: 0.475 Hom.: 10999

Bravo AF: 0.543

Asia WGS AF: 0.235 AC: 824 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 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.27

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: rs7904519; hg19: chr10-114773927;