chr6-132700243-T-C

Variant names:

• chr6-132700243-T-C
• rs2745443
• NM_004666.3:c.342-6061A>G

Variant summary

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

The NM_004666.3(VNN1):​c.342-6061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,980 control chromosomes in the GnomAD database, including 15,718 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 0.44 (15718 hom., cov: 32)
• Consequence: VNN1 NM_004666.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.84
• Publications: 16 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VNN1	NM_004666.3	c.342-6061A>G		intron_variant	Intron 2 of 6	ENST00000367928.5	NP_004657.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VNN1	ENST00000367928.5	c.342-6061A>G		intron_variant	Intron 2 of 6	1	NM_004666.3	ENSP00000356905.4

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66319 AN: 151862 Hom.: 15700 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.437 AC: 66394 AN: 151980 Hom.: 15718 Cov.: 32 AF XY: 0.441 AC XY: 32738 AN XY: 74278

African (AFR) AF: 0.609 AC: 25217 AN: 41426

American (AMR) AF: 0.519 AC: 7933 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2353 AN: 5170

South Asian (SAS) AF: 0.377 AC: 1815 AN: 4820

European-Finnish (FIN) AF: 0.383 AC: 4034 AN: 10536

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22684 AN: 67970

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.363 Hom.: 5932

Bravo AF: 0.454

Asia WGS AF: 0.470 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.44
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2745443; hg19: chr6-133021382;