rs30503

Variant names:

• chr5-134101655-G-C
• rs30503
• NM_001401008.1:c.-7+3808C>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+3808C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,020 control chromosomes in the GnomAD database, including 5,963 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 0.24 (5963 hom., cov: 31)
• Consequence: VDAC1 NM_001401008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VDAC1	NM_001401008.1	c.-7+3808C>G		intron_variant	Intron 2 of 9		NP_001387937.1
VDAC1	NM_001401009.1	c.-4+3808C>G		intron_variant	Intron 2 of 9		NP_001387938.1
VDAC1	NM_001401010.1	c.-130+3808C>G		intron_variant	Intron 2 of 10		NP_001387939.1
VDAC1	NM_001401011.1	c.-275+3808C>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+3808C>G		intron_variant	Intron 2 of 2
ENSG00000309115	ENST00000838696.1	n.402+3808C>G		intron_variant	Intron 2 of 2
ENSG00000309115	ENST00000838697.1	n.171+3808C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36671 AN: 151904 Hom.: 5952 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.242 AC: 36729 AN: 152020 Hom.: 5963 Cov.: 31 AF XY: 0.247 AC XY: 18319 AN XY: 74296

African (AFR) AF: 0.443 AC: 18374 AN: 41440

American (AMR) AF: 0.277 AC: 4235 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1964 AN: 5174

South Asian (SAS) AF: 0.163 AC: 785 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1843 AN: 10556

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8368 AN: 67984

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.180 Hom.: 456

Bravo AF: 0.264

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.49
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs30503; hg19: chr5-133437346;