rs9284788

Variant names:

• chr2-86529157-G-A
• rs9284788
• NM_016079.4:c.286+61C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-86529157-G-A
• chr2-86529157-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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:38847): (RNF103-CHMP3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RNF103 (ring finger protein 103) and CHMP3 (charged multivesicular body protein 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHMP3	NM_016079.4	c.286+61C>T		intron_variant	Intron 3 of 5	ENST00000263856.9	NP_057163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP3	ENST00000263856.9	c.286+61C>T		intron_variant	Intron 3 of 5	1	NM_016079.4	ENSP00000263856.4
RNF103-CHMP3	ENST00000604011.5	c.373+61C>T		intron_variant	Intron 5 of 7	2		ENSP00000474823.1

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

African (AFR) AF: 0.142 AC: 3833 AN: 26934

American (AMR) AF: 0.462 AC: 10475 AN: 22694

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 10014 AN: 19230

East Asian (EAS) AF: 0.706 AC: 23201 AN: 32868

South Asian (SAS) AF: 0.480 AC: 26689 AN: 55590

European-Finnish (FIN) AF: 0.509 AC: 23910 AN: 46948

Middle Eastern (MID) AF: 0.426 AC: 2146 AN: 5042

European-Non Finnish (NFE) AF: 0.469 AC: 477832 AN: 1019458

Other (OTH) AF: 0.461 AC: 24085 AN: 52252

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

African (AFR) AF: 0.151 AC: 6280 AN: 41486

American (AMR) AF: 0.419 AC: 6396 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3861 AN: 5180

South Asian (SAS) AF: 0.490 AC: 2359 AN: 4814

European-Finnish (FIN) AF: 0.509 AC: 5358 AN: 10536

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32084 AN: 67990

Other (OTH) AF: 0.407 AC: 857 AN: 2108

Alfa AF: 0.408 Hom.: 2274

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
PhyloP100		-0.081
Mutation Taster		=17/83	disease causing

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: rs9284788; hg19: chr2-86756280;