chr8-144425879-T-C

Variant names:

• chr8-144425879-T-C
• rs2272658
• NM_016208.4:c.105-107A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS28	NM_016208.4	MANE Select	c.105-107A>G		intron	N/A	NP_057292.1
	VPS28	NM_183057.3		c.105-107A>G		intron	N/A	NP_898880.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS28	ENST00000292510.6	TSL:1 MANE Select	c.105-107A>G		intron	N/A	ENSP00000292510.3
	VPS28	ENST00000377348.6	TSL:1	c.105-107A>G		intron	N/A	ENSP00000366565.2
	VPS28	ENST00000526054.5	TSL:1	c.105-107A>G		intron	N/A	ENSP00000434064.1

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

African (AFR) AF: 0.565 AC: 18368 AN: 32526

American (AMR) AF: 0.576 AC: 22117 AN: 38408

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 15275 AN: 23594

East Asian (EAS) AF: 0.637 AC: 24441 AN: 38388

South Asian (SAS) AF: 0.424 AC: 33620 AN: 79318

European-Finnish (FIN) AF: 0.519 AC: 25108 AN: 48400

Middle Eastern (MID) AF: 0.626 AC: 2927 AN: 4678

European-Non Finnish (NFE) AF: 0.527 AC: 567799 AN: 1077916

Other (OTH) AF: 0.543 AC: 31386 AN: 57830

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

African (AFR) AF: 0.566 AC: 23496 AN: 41488

American (AMR) AF: 0.569 AC: 8710 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2257 AN: 3472

East Asian (EAS) AF: 0.587 AC: 3027 AN: 5154

South Asian (SAS) AF: 0.411 AC: 1981 AN: 4820

European-Finnish (FIN) AF: 0.523 AC: 5539 AN: 10582

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36092 AN: 67954

Other (OTH) AF: 0.538 AC: 1131 AN: 2104

Alfa AF: 0.539 Hom.: 3391

Bravo AF: 0.552

Asia WGS AF: 0.487 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272658; hg19: chr8-145651262;