rs2928378

Positions:

• chr8-144424239-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016208.4(VPS28):​c.432T>C​(p.Arg144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,606,404 control chromosomes in the GnomAD database, including 797,545 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 0.98 (73194 hom., cov: 35)
  • Exomes 𝑓: 1.0 (724351 hom.)
• Consequence: VPS28 NM_016208.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.045 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS28	NM_016208.4	c.432T>C	p.Arg144=	synonymous_variant	8/10	ENST00000292510.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS28	ENST00000292510.6	c.432T>C	p.Arg144=	synonymous_variant	8/10	1	NM_016208.4	P1

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149140 AN: 152204 Hom.: 73146 Cov.: 35

Gnomad AFR AF: 0.930

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.983

GnomAD4 exome AF: 0.998 AC: 1451296 AN: 1454082 Hom.: 724351 Cov.: 89 AF XY: 0.998 AC XY: 721305 AN XY: 722488

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.996

GnomAD4 genome AF: 0.980 AC: 149245 AN: 152322 Hom.: 73194 Cov.: 35 AF XY: 0.980 AC XY: 73001 AN XY: 74478

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.992

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.983

Alfa AF: 0.990 Hom.: 42633

Bravo AF: 0.977

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2928378; hg19: chr8-145649622;