XM_047417635.1:c.-3227C>T

Variant names:

• chr5-134110884-C-T
• rs756699
• XM_047417635.1:c.-3227C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XM_047417635.1(TCF7):​c.-3227C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,230 control chromosomes in the GnomAD database, including 48,967 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 0.80 (48967 hom., cov: 35)
• Consequence: TCF7 XM_047417635.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 46 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]

VDAC1 (HGNC:12669): (voltage dependent anion channel 1) This gene encodes a voltage-dependent anion channel protein that is a major component of the outer mitochondrial membrane. The encoded protein facilitates the exchange of metabolites and ions across the outer mitochondrial membrane and may regulate mitochondrial functions. This protein also forms channels in the plasma membrane and may be involved in transmembrane electron transport. Alternate splicing results in multiple transcript variants. Multiple pseudogenes of this gene are found on chromosomes 1, 2 3, 6, 9, 12, X and Y.[provided by RefSeq, Sep 2010]

ENSG00000309115 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000838695.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC1	NM_001401008.1		c.-175+2718G>A		intron	N/A	NP_001387937.1	A0A1L1UHR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000309115	ENST00000838695.1		n.939+2718G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121576 AN: 152112 Hom.: 48933 Cov.: 35

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.799 AC: 121666 AN: 152230 Hom.: 48967 Cov.: 35 AF XY: 0.794 AC XY: 59104 AN XY: 74414

African (AFR) AF: 0.699 AC: 29032 AN: 41512

American (AMR) AF: 0.771 AC: 11798 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2949 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4406 AN: 5190

South Asian (SAS) AF: 0.744 AC: 3589 AN: 4826

European-Finnish (FIN) AF: 0.788 AC: 8340 AN: 10588

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58759 AN: 68032

Other (OTH) AF: 0.795 AC: 1680 AN: 2114

Alfa AF: 0.834 Hom.: 109219

Bravo AF: 0.794

Asia WGS AF: 0.779 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.68
PhyloP100		1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756699; hg19: chr5-133446575;