rs17653687

Variant names:

• chr5-134132309-A-G
• rs17653687
• NM_003202.5:c.442-5750A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	NM_003202.5	MANE Select	c.442-5750A>G		intron	N/A	NP_003193.2
	TCF7	NM_001346425.2		c.442-5750A>G		intron	N/A	NP_001333354.1
	TCF7	NM_001346450.2		c.97-5750A>G		intron	N/A	NP_001333379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7	ENST00000342854.10	TSL:1 MANE Select	c.442-5750A>G		intron	N/A	ENSP00000340347.5
	TCF7	ENST00000395023.5	TSL:1	c.97-5750A>G		intron	N/A	ENSP00000378469.1
	TCF7	ENST00000518915.5	TSL:1	c.97-5750A>G		intron	N/A	ENSP00000430179.1

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

African (AFR) AF: 0.0595 AC: 2472 AN: 41576

American (AMR) AF: 0.107 AC: 1634 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.0613 AC: 318 AN: 5188

South Asian (SAS) AF: 0.235 AC: 1136 AN: 4832

European-Finnish (FIN) AF: 0.129 AC: 1373 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11538 AN: 68024

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.125 Hom.: 946

Bravo AF: 0.120

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.57
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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