rs225675

Positions:

• chr6-142190999-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016485.5(VTA1):​c.520+1465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,906 control chromosomes in the GnomAD database, including 13,639 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 0.40 (13639 hom., cov: 32)
• Consequence: VTA1 NM_016485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

Genes affected

VTA1 (HGNC:20954): (vesicle trafficking 1) C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005 [PubMed 15644320]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VTA1	NM_016485.5	c.520+1465A>G		intron_variant		ENST00000367630.9
VTA1	NM_001286371.2	c.520+1465A>G		intron_variant
VTA1	NM_001286372.2	c.346+1465A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTA1	ENST00000367630.9	c.520+1465A>G		intron_variant		1	NM_016485.5	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60286 AN: 151788 Hom.: 13641 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.397 AC: 60293 AN: 151906 Hom.: 13639 Cov.: 32 AF XY: 0.395 AC XY: 29327 AN XY: 74240

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.389

Alfa AF: 0.438 Hom.: 2014

Bravo AF: 0.368

Asia WGS AF: 0.280 AC: 978 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.096
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs225675; hg19: chr6-142512136;