Variant chr10-112951635-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367943.1(TCF7L2):c.381+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,104,254 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 149 hom., cov: 22)

Exomes 𝑓: 0.0025 ( 120 hom. )

Consequence

TCF7L2
NM_001367943.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.129

Variant links:

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 links:

ENSG00000233547 (HGNC:):

ENSG00000233547 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-112951635-C-A is Benign according to our data. Variant chr10-112951635-C-A is described in ClinVar as [Benign]. Clinvar id is 1220588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 linkuse as main transcript	c.381+28C>A		intron_variant		ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 linkuse as main transcript	c.381+28C>A		intron_variant		1	NM_001367943.1	ENSP00000348274.4		Q9NQB0-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3139

AN:

142114

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00913

Gnomad ASJ

AF:

0.00209

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00336

Gnomad NFE

AF:

0.000216

Gnomad OTH

AF:

0.0159

GnomAD3 exomes

AF:

0.00751

AC:

227

AN:

30234

Hom.:

AF XY:

0.00527

AC XY:

AN XY:

17822

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.00886

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000590

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.00254

AC:

2445

AN:

962068

Hom.:

120

Cov.:

AF XY:

0.00237

AC XY:

1095

AN XY:

461054

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.00208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000446

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00670

GnomAD4 genome

AF:

0.0221

AC:

3145

AN:

142186

Hom.:

149

Cov.:

AF XY:

0.0209

AC XY:

1449

AN XY:

69190

show subpopulations

Gnomad4 AFR

AF:

0.0774

Gnomad4 AMR

AF:

0.00906

Gnomad4 ASJ

AF:

0.00209

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000216

Gnomad4 OTH

AF:

0.0158

Alfa

AF:

0.000429

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over