rs30499

Variant names:

• chr5-134106035-C-T
• rs30499
• NM_001401009.1:c.-327G>A

Variant summary

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

The NM_001401009.1(VDAC1):​c.-327G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,156 control chromosomes in the GnomAD database, including 35,354 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 0.67 (35354 hom., cov: 33)
• Consequence: VDAC1 NM_001401009.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDAC1	NM_001401009.1	c.-327G>A		5_prime_UTR_variant	Exon 1 of 10		NP_001387938.1
VDAC1	NM_001401010.1	c.-453G>A		5_prime_UTR_variant	Exon 1 of 11		NP_001387939.1
VDAC1	NM_001401011.1	c.-598G>A		5_prime_UTR_variant	Exon 1 of 12		NP_001387940.1
VDAC1	NM_001401008.1	c.-174-405G>A		intron_variant	Intron 1 of 9		NP_001387937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309115	ENST00000838695.1	n.940-405G>A		intron_variant	Intron 1 of 2
ENSG00000309115	ENST00000838696.1	n.235-405G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102251 AN: 152038 Hom.: 35348 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.672 AC: 102296 AN: 152156 Hom.: 35354 Cov.: 33 AF XY: 0.664 AC XY: 49396 AN XY: 74412

African (AFR) AF: 0.542 AC: 22485 AN: 41480

American (AMR) AF: 0.628 AC: 9605 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2533 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2385 AN: 5172

South Asian (SAS) AF: 0.596 AC: 2878 AN: 4826

European-Finnish (FIN) AF: 0.705 AC: 7464 AN: 10592

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52463 AN: 68000

Other (OTH) AF: 0.686 AC: 1450 AN: 2114

Alfa AF: 0.724 Hom.: 73398

Bravo AF: 0.660

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.83
DANN	Benign	0.47
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs30499; hg19: chr5-133441726;