rs2745426

Positions:

• chr6-132682205-C-T

Variant summary

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

The NM_004666.3(VNN1):​c.*935G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,016 control chromosomes in the GnomAD database, including 11,975 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 0.38 (11975 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: VNN1 NM_004666.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

VNN1 (HGNC:12705): (vanin 1) This gene encodes a member of the vanin family of proteins, which 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. This protein, like its mouse homolog, is likely a GPI-anchored cell surface molecule. The mouse protein is expressed by the perivascular thymic stromal cells and regulates migration of T-cell progenitors to the thymus. This gene lies in close proximity to, and in the same transcriptional orientation as, two other vanin genes on chromosome 6q23-q24. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VNN1	NM_004666.3	c.*935G>A		3_prime_UTR_variant	7/7	ENST00000367928.5	NP_004657.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VNN1	ENST00000367928.5	c.*935G>A		3_prime_UTR_variant	7/7	1	NM_004666.3	ENSP00000356905	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57421 AN: 151900 Hom.: 11959 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.377

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.378 AC: 57479 AN: 152016 Hom.: 11975 Cov.: 32 AF XY: 0.378 AC XY: 28109 AN XY: 74320

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.377

Alfa AF: 0.308 Hom.: 13035

Bravo AF: 0.388

Asia WGS AF: 0.317 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.76

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: rs2745426; hg19: chr6-133003344;