Variant chr10-112951918-C-T 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+311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,218 control chromosomes in the GnomAD database, including 24,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24024 hom., cov: 27)

Exomes 𝑓: 0.44 ( 77 hom. )

Consequence

TCF7L2
NM_001367943.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.466

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:

LOC124902502 (HGNC:):

LOC124902502 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-112951918-C-T is Benign according to our data. Variant chr10-112951918-C-T is described in ClinVar as [Benign]. Clinvar id is 1248694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1 linkuse as main transcript	c.381+311C>T		intron_variant		ENST00000355995.9
LOC124902502	XR_007062291.1 linkuse as main transcript	n.425G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9 linkuse as main transcript	c.381+311C>T		intron_variant		1	NM_001367943.1		Q9NQB0-1
	ENST00000369391.3 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

84545

AN:

150470

Hom.:

23997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.443

AC:

279

AN:

630

Hom.:

Cov.:

AF XY:

0.484

AC XY:

206

AN XY:

426

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.455

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.462

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.562

AC:

84620

AN:

150588

Hom.:

24024

Cov.:

AF XY:

0.556

AC XY:

40854

AN XY:

73508

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.592

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.577

Alfa

AF:

0.553

Hom.:

2595

Bravo

AF:

0.572

Asia WGS

AF:

0.433

AC:

1498

AN:

3466

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	clinical testing	GeneDx	Jun 14, 2019	- -
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

-0.67

CADD

Benign

DANN

Benign

0.65

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