8-81741409-A-G

Position:

• chr8-81741409-A-G

Variant summary

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

The NM_152284.4(CHMP4C):​c.190+8593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,196 control chromosomes in the GnomAD database, including 328 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 0.065 (328 hom., cov: 32)
• Consequence: CHMP4C NM_152284.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

Genes affected

CHMP4C (HGNC:30599): (charged multivesicular body protein 4C) CHMP4C 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP4C	NM_152284.4	c.190+8593A>G		intron_variant		ENST00000297265.5	NP_689497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP4C	ENST00000297265.5	c.190+8593A>G		intron_variant		1	NM_152284.4	ENSP00000297265	P1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9889 AN: 152078 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0650 AC: 9898 AN: 152196 Hom.: 328 Cov.: 32 AF XY: 0.0638 AC XY: 4752 AN XY: 74428

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.0866

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0705 Hom.: 547

Bravo AF: 0.0636

Asia WGS AF: 0.0310 AC: 107 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.81

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: rs11782652; hg19: chr8-82653644;