rs2272658

Positions:

• chr8-144425879-T-C
• chr8-144425879-T-G

Variant summary

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

The NM_016208.4(VPS28):​c.105-107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,553,136 control chromosomes in the GnomAD database, including 220,119 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 0.54 (22701 hom., cov: 33)
  • Exomes 𝑓: 0.53 (197418 hom.)
• Consequence: VPS28 NM_016208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

Genes affected

VPS28 (HGNC:18178): (VPS28 subunit of ESCRT-I) This gene encodes a protein subunit of the ESCRT-I complex (endosomal complexes required for transport), which functions in the transport and sorting of proteins into subcellular vesicles. This complex can also be hijacked to facilitate the budding of enveloped viruses from the cell membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS28	NM_016208.4	c.105-107A>G		intron_variant		ENST00000292510.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS28	ENST00000292510.6	c.105-107A>G		intron_variant		1	NM_016208.4	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82785 AN: 151960 Hom.: 22682 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.529 AC: 741041 AN: 1401058 Hom.: 197418 Cov.: 50 AF XY: 0.526 AC XY: 362664 AN XY: 689808

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.637

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.545 AC: 82860 AN: 152078 Hom.: 22701 Cov.: 33 AF XY: 0.545 AC XY: 40514 AN XY: 74338

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.538

Alfa AF: 0.538 Hom.: 3265

Bravo AF: 0.552

Asia WGS AF: 0.487 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.57

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: rs2272658; hg19: chr8-145651262;