rs30500

Variant names:

• chr5-134104185-T-C
• rs30500
• NM_001401008.1:c.-7+1278A>G

Variant summary

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

The NM_001401008.1(VDAC1):​c.-7+1278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,166 control chromosomes in the GnomAD database, including 44,502 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 0.76 (44502 hom., cov: 33)
• Consequence: VDAC1 NM_001401008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 6 publications found

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]

ENSG00000309115 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDAC1	NM_001401008.1	c.-7+1278A>G		intron_variant	Intron 2 of 9		NP_001387937.1
VDAC1	NM_001401009.1	c.-4+1278A>G		intron_variant	Intron 2 of 9		NP_001387938.1
VDAC1	NM_001401010.1	c.-130+1278A>G		intron_variant	Intron 2 of 10		NP_001387939.1
VDAC1	NM_001401011.1	c.-275+1278A>G		intron_variant	Intron 2 of 11		NP_001387940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309115	ENST00000838695.1	n.1107+1278A>G		intron_variant	Intron 2 of 2
ENSG00000309115	ENST00000838696.1	n.402+1278A>G		intron_variant	Intron 2 of 2
ENSG00000309115	ENST00000838697.1	n.171+1278A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115576 AN: 152048 Hom.: 44471 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.760 AC: 115666 AN: 152166 Hom.: 44502 Cov.: 33 AF XY: 0.757 AC XY: 56349 AN XY: 74398

African (AFR) AF: 0.667 AC: 27692 AN: 41500

American (AMR) AF: 0.775 AC: 11861 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2701 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2771 AN: 5160

South Asian (SAS) AF: 0.700 AC: 3378 AN: 4824

European-Finnish (FIN) AF: 0.832 AC: 8824 AN: 10606

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55703 AN: 67988

Other (OTH) AF: 0.782 AC: 1649 AN: 2110

Alfa AF: 0.797 Hom.: 162125

Bravo AF: 0.751

Asia WGS AF: 0.648 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs30500; hg19: chr5-133439876;