XM_047417635.1:c.-4741A>G

Variant names:

• chr5-134109370-A-G
• rs244948
• XM_047417635.1:c.-4741A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047417635.1(TCF7):​c.-4741A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,118 control chromosomes in the GnomAD database, including 49,033 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 (49033 hom., cov: 32)
• Consequence: TCF7 XM_047417635.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7	XM_047417635.1	c.-4741A>G		5_prime_UTR_variant	Exon 1 of 10		XP_047273591.1
TCF7	XM_047417634.1	c.-4741A>G		5_prime_UTR_variant	Exon 1 of 11		XP_047273590.1
TCF7	XM_047417636.1	c.-4741A>G		5_prime_UTR_variant	Exon 1 of 12		XP_047273592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309115	ENST00000838695.1	n.940-3740T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121609 AN: 152000 Hom.: 48999 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.800 AC: 121699 AN: 152118 Hom.: 49033 Cov.: 32 AF XY: 0.795 AC XY: 59116 AN XY: 74358

African (AFR) AF: 0.699 AC: 28998 AN: 41460

American (AMR) AF: 0.772 AC: 11791 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3011 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4417 AN: 5186

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

European-Finnish (FIN) AF: 0.787 AC: 8330 AN: 10578

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58761 AN: 68004

Other (OTH) AF: 0.799 AC: 1683 AN: 2106

Alfa AF: 0.843 Hom.: 184266

Bravo AF: 0.795

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.33
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs244948; hg19: chr5-133445061;