5-134107188-T-C

Variant names:

• chr5-134107188-T-C
• rs30496
• NM_001401008.1:c.-174-1558A>G

Variant summary

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

The NM_001401008.1(VDAC1):​c.-174-1558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,304 control chromosomes in the GnomAD database, including 64,746 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 0.92 (64746 hom., cov: 33)
• Consequence: VDAC1 NM_001401008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88

Genes affected

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDAC1	NM_001401008.1	c.-174-1558A>G		intron_variant	Intron 1 of 9		NP_001387937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140180 AN: 152186 Hom.: 64680 Cov.: 33

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.919

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

GnomAD4 genome AF: 0.921 AC: 140307 AN: 152304 Hom.: 64746 Cov.: 33 AF XY: 0.919 AC XY: 68448 AN XY: 74460

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.919

Alfa AF: 0.887 Hom.: 3288

Bravo AF: 0.930

Asia WGS AF: 0.884 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs30496; hg19: chr5-133442879;