rs9284788

chr2-86529157-G-A

Variant summary

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

The NM_016079.4(CHMP3):c.286+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,433,074 control chromosomes in the GnomAD database, including 158,205 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 0.39 (13607 hom., cov: 32)
  • Exomes 𝑓: 0.47 (144598 hom.)
• Consequence: CHMP3 NM_016079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

CHMP3 (HGNC:29865): (charged multivesicular body protein 3) This gene encodes a protein that sorts transmembrane proteins into lysosomes/vacuoles via the multivesicular body (MVB) pathway. This protein, along with other soluble coiled-coil containing proteins, forms part of the ESCRT-III protein complex that binds to the endosomal membrane and recruits additional cofactors for protein sorting into the MVB. This protein may also co-immunoprecipitate with a member of the IFG-binding protein superfamily. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ring finger protein 103 (RNF103) gene. [provided by RefSeq, Nov 2010]

RNF103-CHMP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP3	NM_016079.4	c.286+61C>T		intron_variant		ENST00000263856.9
RNF103-CHMP3	NM_001198954.1	c.373+61C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP3	ENST00000263856.9	c.286+61C>T		intron_variant		1	NM_016079.4	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59437 AN: 151940 Hom.: 13602 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.470 AC: 602185 AN: 1281016 Hom.: 144598 AF XY: 0.471 AC XY: 294749 AN XY: 625876

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.706

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.391 AC: 59450 AN: 152058 Hom.: 13607 Cov.: 32 AF XY: 0.395 AC XY: 29364 AN XY: 74308

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.407

Alfa AF: 0.416 Hom.: 2261

Bravo AF: 0.376

Asia WGS AF: 0.544 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.7
Dann	Benign	0.79

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: rs9284788; hg19: chr2-86756280;