5-134109370-A-G

Variant names:

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

Variant summary

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

The NM_001401008.1(VDAC1):​c.-174-3740T>C variant causes a intron 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: VDAC1 NM_001401008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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]

ACMG classification

Verdict is Benign. Variant got -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

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

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.799

Alfa AF: 0.849 Hom.: 65882

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs244948; hg19: chr5-133445061;