rs12211125

chr6-132743910-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004665.6(VNN2):c.*390A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 155,124 control chromosomes in the GnomAD database, including 541 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 0.069 (525 hom., cov: 32)
  • Exomes 𝑓: 0.079 (16 hom.)
• Consequence: VNN2 NM_004665.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

VNN2 (HGNC:12706): (vanin 2) This gene product is a member of the Vanin family of proteins that share extensive sequence similarity with each other, and also with biotinidase. The family includes secreted and membrane-associated proteins, a few of which have been reported to participate in hematopoietic cell trafficking. No biotinidase activity has been demonstrated for any of the vanin proteins, however, they possess pantetheinase activity, which may play a role in oxidative-stress response. The encoded protein is a GPI-anchored cell surface molecule that plays a role in transendothelial migration of neutrophils. This gene lies in close proximity to, and in same transcriptional orientation as two other vanin genes on chromosome 6q23-q24. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VNN2	NM_004665.6	c.*390A>G		3_prime_UTR_variant	7/7	ENST00000326499.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN2	ENST00000326499.11	c.*390A>G		3_prime_UTR_variant	7/7	1	NM_004665.6	P1
VNN2	ENST00000418593.6	c.*1081A>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	1
VNN2	ENST00000422400.6	c.*1207A>G		3_prime_UTR_variant, NMD_transcript_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10514 AN: 152128 Hom.: 525 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0855

GnomAD4 exome AF: 0.0785 AC: 226 AN: 2878 Hom.: 16 Cov.: 0 AF XY: 0.0701 AC XY: 105 AN XY: 1498

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0803

Gnomad4 OTH exome AF: 0.0802

GnomAD4 genome AF: 0.0691 AC: 10515 AN: 152246 Hom.: 525 Cov.: 32 AF XY: 0.0702 AC XY: 5222 AN XY: 74420

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0985

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0845 Hom.: 726

Bravo AF: 0.0717

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12211125; hg19: chr6-133065049;