rs151822

Positions:

• chr5-134120270-G-A
• chr5-134120270-G-T

Variant summary

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

The NM_003202.5(TCF7):​c.441+4237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,054 control chromosomes in the GnomAD database, including 33,040 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 0.64 (33040 hom., cov: 32)
• Consequence: TCF7 NM_003202.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7	NM_003202.5	c.441+4237G>A		intron_variant		ENST00000342854.10	NP_003193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7	ENST00000342854.10	c.441+4237G>A		intron_variant		1	NM_003202.5	ENSP00000340347.5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97822 AN: 151938 Hom.: 33040 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.644 AC: 97851 AN: 152054 Hom.: 33040 Cov.: 32 AF XY: 0.635 AC XY: 47165 AN XY: 74326

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.654

Alfa AF: 0.733 Hom.: 18706

Bravo AF: 0.623

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs151822; hg19: chr5-133455961;