5-134107188-T-C

Variant names:

• chr5-134107188-T-C
• rs30496
• NM_001401008.1:c.-174-1558A>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.-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
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001401008.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC1	NM_001401008.1		c.-174-1558A>G		intron	N/A	NP_001387937.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000309115	ENST00000838696.1		n.183A>G		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000309115	ENST00000838695.1		n.940-1558A>G		intron	N/A

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

African (AFR) AF: 0.981 AC: 40779 AN: 41588

American (AMR) AF: 0.923 AC: 14122 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.931 AC: 4814 AN: 5172

South Asian (SAS) AF: 0.825 AC: 3977 AN: 4818

European-Finnish (FIN) AF: 0.885 AC: 9395 AN: 10612

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 60992 AN: 68020

Other (OTH) AF: 0.919 AC: 1945 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.39
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs30496; hg19: chr5-133442879;