Variant 6-132692587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004666.3(VNN1):c.827-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,555,458 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 195 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 181 hom. )

Consequence

VNN1
NM_004666.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003056

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.984

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-132692587-G-A is Benign according to our data. Variant chr6-132692587-G-A is described in ClinVar as [Benign]. Clinvar id is 776160.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VNN1	NM_004666.3 linkuse as main transcript	c.827-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VNN1	ENST00000367928.5 linkuse as main transcript	c.827-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004666.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4225

AN:

152082

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.00782

AC:

1569

AN:

200714

Hom.:

AF XY:

0.00574

AC XY:

630

AN XY:

109778

show subpopulations

Gnomad AFR exome

AF:

0.0962

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00278

AC:

3907

AN:

1403260

Hom.:

181

Cov.:

AF XY:

0.00245

AC XY:

1705

AN XY:

694540

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.0279

AC:

4240

AN:

152198

Hom.:

195

Cov.:

AF XY:

0.0266

AC XY:

1976

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0971

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.0

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over