rs30500

Positions:

• chr5-134104185-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
VDAC1	NM_001401008.1	c.-7+1278A>G		intron_variant			NP_001387937.1
VDAC1	NM_001401009.1	c.-4+1278A>G		intron_variant			NP_001387938.1
VDAC1	NM_001401010.1	c.-130+1278A>G		intron_variant			NP_001387939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.782

Alfa AF: 0.805 Hom.: 61387

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs30500; hg19: chr5-133439876;