rs2928378

Variant names:

• chr8-144424239-A-G
• rs2928378
• NM_016208.4:c.432T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016208.4(VPS28):​c.432T>C​(p.Arg144Arg) 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VPS28	NM_016208.4	c.432T>C	p.Arg144Arg	synonymous_variant	Exon 8 of 10	ENST00000292510.6	NP_057292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS28	ENST00000292510.6	c.432T>C	p.Arg144Arg	synonymous_variant	Exon 8 of 10	1	NM_016208.4	ENSP00000292510.3

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

African (AFR) AF: 0.929 AC: 30880 AN: 33234

American (AMR) AF: 0.997 AC: 43790 AN: 43942

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25866 AN: 25866

East Asian (EAS) AF: 1.00 AC: 39516 AN: 39516

South Asian (SAS) AF: 1.00 AC: 85657 AN: 85672

European-Finnish (FIN) AF: 1.00 AC: 52941 AN: 52942

Middle Eastern (MID) AF: 0.999 AC: 5580 AN: 5588

European-Non Finnish (NFE) AF: 1.00 AC: 1107298 AN: 1107332

Other (OTH) AF: 0.996 AC: 59768 AN: 59990

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

African (AFR) AF: 0.930 AC: 38639 AN: 41544

American (AMR) AF: 0.992 AC: 15181 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.999 AC: 4827 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68029 AN: 68034

Other (OTH) AF: 0.983 AC: 2079 AN: 2114

Alfa AF: 0.989 Hom.: 58970

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
PhyloP100		0.045

Splicing

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

Other links and lift over

dbSNP: rs2928378; hg19: chr8-145649622;