rs11543

Variant names:

• chr10-75210855-G-C
• rs11543
• NM_001391963.1:c.-109G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-75210855-G-C
• chr10-75210855-G-T

Variant summary

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

The NM_001391963.1(VDAC2):​c.-109G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 328,884 control chromosomes in the GnomAD database, including 72,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.69 (38630 hom., cov: 33)
  • Exomes 𝑓: 0.60 (34273 hom.)
• Consequence: VDAC2 NM_001391963.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 12 publications found

Genes affected

VDAC2 (HGNC:12672): (voltage dependent anion channel 2) This gene encodes a member of the voltage-dependent anion channel pore-forming family of proteins that are considered the main pathway for metabolite diffusion across the mitochondrial outer membrane. The encoded protein is also thought to be involved in the mitochondrial apoptotic pathway via regulation of BCL2-antagonist/killer 1 protein activity. Pseudogenes have been identified on chromosomes 1, 2, 12 and 21, and alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ENSG00000296693 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391963.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC2	NM_001391963.1	MANE Select	c.-109G>C		5_prime_UTR	Exon 1 of 10	NP_001378892.1	A0A024QZT0
	VDAC2	NM_001184783.3		c.-242G>C		5_prime_UTR	Exon 2 of 12	NP_001171712.1	P45880-1
	VDAC2	NM_003375.5		c.-109G>C		5_prime_UTR	Exon 2 of 11	NP_003366.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VDAC2	ENST00000332211.11	TSL:1 MANE Select	c.-109G>C		5_prime_UTR	Exon 1 of 10	ENSP00000361686.3	P45880-3
	VDAC2	ENST00000313132.8	TSL:1	c.-242G>C		5_prime_UTR	Exon 1 of 11	ENSP00000361635.1	P45880-1
	VDAC2	ENST00000958959.1		c.-109G>C		5_prime_UTR	Exon 1 of 12	ENSP00000629018.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104877 AN: 151946 Hom.: 38567 Cov.: 33

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.702

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.699

GnomAD4 exome AF: 0.604 AC: 106780 AN: 176820 Hom.: 34273 Cov.: 2 AF XY: 0.603 AC XY: 54768 AN XY: 90876

African (AFR) AF: 0.908 AC: 4480 AN: 4934

American (AMR) AF: 0.769 AC: 3668 AN: 4770

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 3365 AN: 6642

East Asian (EAS) AF: 0.964 AC: 14898 AN: 15454

South Asian (SAS) AF: 0.782 AC: 4107 AN: 5250

European-Finnish (FIN) AF: 0.515 AC: 7431 AN: 14428

Middle Eastern (MID) AF: 0.696 AC: 656 AN: 942

European-Non Finnish (NFE) AF: 0.540 AC: 60904 AN: 112850

Other (OTH) AF: 0.630 AC: 7271 AN: 11550

GnomAD4 genome AF: 0.690 AC: 104996 AN: 152064 Hom.: 38630 Cov.: 33 AF XY: 0.695 AC XY: 51651 AN XY: 74338

African (AFR) AF: 0.920 AC: 38237 AN: 41544

American (AMR) AF: 0.749 AC: 11446 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3472

East Asian (EAS) AF: 0.962 AC: 4948 AN: 5144

South Asian (SAS) AF: 0.815 AC: 3933 AN: 4828

European-Finnish (FIN) AF: 0.517 AC: 5468 AN: 10576

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.546 AC: 37053 AN: 67908

Other (OTH) AF: 0.702 AC: 1481 AN: 2110

Alfa AF: 0.447 Hom.: 1098

Bravo AF: 0.715

Asia WGS AF: 0.902 AC: 3129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		-0.53
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11543; hg19: chr10-76970613;