rs4897612

Variant names:

• chr6-132714186-A-C
• rs4897612
• ENST00000886805.1:c.-18-133T>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 4P and 9B. PVS1_Strong BP6 BA1

The ENST00000886808.1(VNN1):​c.-19+2T>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 683,500 control chromosomes in the GnomAD database, including 64,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.52 (23806 hom., cov: 32)
  • Exomes 𝑓: 0.38 (40847 hom.)
• Consequence: VNN1 ENST00000886808.1 splice_donor, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.25
• Publications: 11 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: Likely_benign. The variant received -5 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.22762646 fraction of the gene.
• BP6: Variant 6-132714186-A-C is Benign according to our data. Variant chr6-132714186-A-C is described in ClinVar as Benign. ClinVar VariationId is 6230.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000886808.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN1	NM_004666.3	MANE Select	c.-151T>G		upstream_gene	N/A	NP_004657.2	O95497

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VNN1	ENST00000886805.1		c.-18-133T>G		intron	N/A	ENSP00000556864.1
	VNN1	ENST00000886806.1		c.-18-133T>G		intron	N/A	ENSP00000556865.1
	VNN1	ENST00000886807.1		c.-18-133T>G		intron	N/A	ENSP00000556866.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78327 AN: 151988 Hom.: 23755 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.376 AC: 199819 AN: 531394 Hom.: 40847 AF XY: 0.378 AC XY: 104347 AN XY: 275692

African (AFR) AF: 0.841 AC: 11517 AN: 13696

American (AMR) AF: 0.563 AC: 10139 AN: 17998

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 4382 AN: 14236

East Asian (EAS) AF: 0.371 AC: 11616 AN: 31352

South Asian (SAS) AF: 0.456 AC: 20703 AN: 45446

European-Finnish (FIN) AF: 0.409 AC: 12109 AN: 29596

Middle Eastern (MID) AF: 0.346 AC: 856 AN: 2474

European-Non Finnish (NFE) AF: 0.336 AC: 117064 AN: 347968

Other (OTH) AF: 0.399 AC: 11433 AN: 28628

GnomAD4 genome AF: 0.516 AC: 78445 AN: 152106 Hom.: 23806 Cov.: 32 AF XY: 0.519 AC XY: 38596 AN XY: 74342

African (AFR) AF: 0.845 AC: 35079 AN: 41510

American (AMR) AF: 0.552 AC: 8436 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1978 AN: 5168

South Asian (SAS) AF: 0.473 AC: 2284 AN: 4832

European-Finnish (FIN) AF: 0.430 AC: 4554 AN: 10580

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23594 AN: 67960

Other (OTH) AF: 0.510 AC: 1079 AN: 2114

Alfa AF: 0.501 Hom.: 4190

Bravo AF: 0.537

Asia WGS AF: 0.512 AC: 1784 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RECLASSIFIED - VNN1 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.53
PhyloP100		-2.3
PromoterAI		0.12	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4897612; hg19: chr6-133035325;