6-132751295-T-C

Variant names:

• chr6-132751295-T-C
• rs33961621
• NM_004665.6:c.1050A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_004665.6(VNN2):​c.1050A>G​(p.Glu350Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,130 control chromosomes in the GnomAD database, including 48 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 0.011 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (25 hom.)
• Consequence: VNN2 NM_004665.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1659/152260) while in subpopulation AFR AF= 0.0352 (1463/41528). AF 95% confidence interval is 0.0337. There are 23 homozygotes in gnomad4. There are 759 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VNN2	NM_004665.6	c.1050A>G	p.Glu350Glu	synonymous_variant	Exon 5 of 7	ENST00000326499.11	NP_004656.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VNN2	ENST00000326499.11	c.1050A>G	p.Glu350Glu	synonymous_variant	Exon 5 of 7	1	NM_004665.6	ENSP00000322276.6

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1655 AN: 152142 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00292 AC: 734 AN: 251242 Hom.: 9 AF XY: 0.00230 AC XY: 312 AN XY: 135806

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00125 AC: 1826 AN: 1461870 Hom.: 25 Cov.: 31 AF XY: 0.00106 AC XY: 772 AN XY: 727234

Gnomad4 AFR exome AF: 0.0351

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.0109 AC: 1659 AN: 152260 Hom.: 23 Cov.: 32 AF XY: 0.0102 AC XY: 759 AN XY: 74466

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00444 Hom.: 6

Bravo AF: 0.0121

EpiCase AF: 0.000273

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.69
DANN	Benign	0.87

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: rs33961621; hg19: chr6-133072434;