rs12527885

Variant names:

• chr6-132708303-A-G
• rs12527885
• NM_004666.3:c.341+3406T>C

Variant summary

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

The NM_004666.3(VNN1):​c.341+3406T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,198 control chromosomes in the GnomAD database, including 1,632 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 0.12 (1632 hom., cov: 32)
• Consequence: VNN1 NM_004666.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VNN1	NM_004666.3	c.341+3406T>C		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.341+3406T>C		intron_variant	Intron 2 of 6	1	NM_004666.3	ENSP00000356905.4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18478 AN: 152080 Hom.: 1626 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0785

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.122 AC: 18516 AN: 152198 Hom.: 1632 Cov.: 32 AF XY: 0.126 AC XY: 9406 AN XY: 74396

African (AFR) AF: 0.221 AC: 9189 AN: 41518

American (AMR) AF: 0.167 AC: 2545 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0785 AC: 272 AN: 3466

East Asian (EAS) AF: 0.126 AC: 655 AN: 5190

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4816

European-Finnish (FIN) AF: 0.0878 AC: 930 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0513 AC: 3492 AN: 68020

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.0950 Hom.: 179

Bravo AF: 0.131

Asia WGS AF: 0.209 AC: 728 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		1.5
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: rs12527885; hg19: chr6-133029442;