Variant 10-112951574-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001367943.1(TCF7L2):c.348C>T(p.Leu116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,372,036 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 29)

Exomes 𝑓: 0.0024 ( 10 hom. )

Consequence

TCF7L2
NM_001367943.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.112

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-112951574-C-T is Benign according to our data. Variant chr10-112951574-C-T is described in ClinVar as [Benign]. Clinvar id is 770593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.112 with no splicing effect.

BS2

High AC in GnomAd4 at 284 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 linkuse as main transcript	c.348C>T	p.Leu116=	synonymous_variant	3/15	ENST00000355995.9	NP_001354872.1
LOC124902502	XR_007062291.1 linkuse as main transcript	n.565+204G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 linkuse as main transcript	c.348C>T	p.Leu116=	synonymous_variant	3/15	1	NM_001367943.1	ENSP00000348274		Q9NQB0-1
	ENST00000369391.3 linkuse as main transcript	n.98+204G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

285

AN:

148218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000342

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00475

Gnomad ASJ

AF:

0.00441

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00669

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00293

GnomAD3 exomes

AF:

0.00246

AC:

460

AN:

187140

Hom.:

AF XY:

0.00299

AC XY:

312

AN XY:

104380

show subpopulations

Gnomad AFR exome

AF:

0.000505

Gnomad AMR exome

AF:

0.00233

Gnomad ASJ exome

AF:

0.00364

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00736

Gnomad FIN exome

AF:

0.0000494

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00241

AC:

2947

AN:

1223710

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1576

AN XY:

608890

show subpopulations

Gnomad4 AFR exome

AF:

0.000286

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00404

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00716

Gnomad4 FIN exome

AF:

0.0000482

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00191

AC:

284

AN:

148326

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

129

AN XY:

72298

show subpopulations

Gnomad4 AFR

AF:

0.000341

Gnomad4 AMR

AF:

0.00475

Gnomad4 ASJ

AF:

0.00441

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00649

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00290

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00208

Asia WGS

AF:

0.00214

AC:

AN:

3284

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	TCF7L2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 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

-0.64

CADD

Benign

DANN

Benign

0.93

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