rs844239

Positions:

• chr9-33270481-A-G
• chr9-33270481-A-T

Variant summary

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

The NM_016410.6(CHMP5):​c.222-142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 643,054 control chromosomes in the GnomAD database, including 172,302 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 0.64 (34382 hom., cov: 32)
  • Exomes 𝑓: 0.75 (137920 hom.)
• Consequence: CHMP5 NM_016410.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

Genes affected

CHMP5 (HGNC:26942): (charged multivesicular body protein 5) CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP5	NM_016410.6	c.222-142A>G		intron_variant		ENST00000223500.9	NP_057494.3
CHMP5	NM_001195536.2	c.222-142A>G		intron_variant			NP_001182465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP5	ENST00000223500.9	c.222-142A>G		intron_variant		1	NM_016410.6	ENSP00000223500.7
CHMP5	ENST00000419016.6	c.222-142A>G		intron_variant		2		ENSP00000442725.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97923 AN: 151792 Hom.: 34380 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.903

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.667

GnomAD4 exome AF: 0.745 AC: 366048 AN: 491146 Hom.: 137920 AF XY: 0.745 AC XY: 193445 AN XY: 259544

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.759

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.736

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.645 AC: 97946 AN: 151908 Hom.: 34382 Cov.: 32 AF XY: 0.650 AC XY: 48268 AN XY: 74268

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.668

Alfa AF: 0.683 Hom.: 4444

Bravo AF: 0.625

Asia WGS AF: 0.668 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.012
DANN	Benign	0.66

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: rs844239; hg19: chr9-33270479; COSMIC: COSV56302750;