rs17653687

Positions:

• chr5-134132309-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003202.5(TCF7):​c.442-5750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,322 control chromosomes in the GnomAD database, including 1,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1496 hom., cov: 33)
• Consequence: TCF7 NM_003202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

Genes affected

TCF7 (HGNC:11639): (transcription factor 7) This gene encodes a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators. This gene is expressed predominantly in T-cells and plays a critical role in natural killer cell and innate lymphoid cell development. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/beta-catenin signaling pathway. Mice with a knockout of this gene are viable and fertile, but display a block in T-lymphocyte differentiation. Alternative splicing results in multiple transcript variants. Naturally-occurring isoforms lacking the N-terminal beta-catenin interaction domain may act as dominant negative regulators of Wnt signaling. [provided by RefSeq, Oct 2016]

TCF7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7	NM_003202.5	c.442-5750A>G		intron_variant		ENST00000342854.10	NP_003193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7	ENST00000342854.10	c.442-5750A>G		intron_variant		1	NM_003202.5	ENSP00000340347.5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19521 AN: 152204 Hom.: 1495 Cov.: 33

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.128 AC: 19524 AN: 152322 Hom.: 1496 Cov.: 33 AF XY: 0.126 AC XY: 9407 AN XY: 74492

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0613

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.122

Alfa AF: 0.138 Hom.: 365

Bravo AF: 0.120

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.57

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: rs17653687; hg19: chr5-133468000; COSMIC: COSV58659073;