ENST00000886805.1:c.-18-133T>G – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000886805.1(VNN1):c.-18-133T>G variant causes a 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
ENST00000886805.1 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.25

Publications

11 publications found

Variant links:

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]

VNN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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: ENST00000886805.1. 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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
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.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5627

11255

16882

22510

28137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1672

3344

5016

6688

8360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.516

AC:

78445

AN:

152106

Hom.:

23806

Cov.:

AF XY:

0.519

AC XY:

38596

AN XY:

74342

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1620

3239

4859

6478

8098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

RECLASSIFIED - VNN1 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.34

(source)

DANN

Benign

0.53

PhyloP100

-2.3

PromoterAI

0.12

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over