rs2280934

Positions:

• chr8-23249152-A-G

Variant summary

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

The NM_152272.5(CHMP7):​c.300-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,398,606 control chromosomes in the GnomAD database, including 122,617 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 0.35 (10648 hom., cov: 32)
  • Exomes 𝑓: 0.42 (111969 hom.)
• Consequence: CHMP7 NM_152272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

CHMP7 (HGNC:28439): (charged multivesicular body protein 7) Involved in several processes, including late endosome to vacuole transport; midbody abscission; and mitotic nuclear division. Located in cytosol; nuclear envelope; and nucleoplasm. Part of ESCRT III complex. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.300-58A>G		intron_variant		ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.300-58A>G		intron_variant		1	NM_152272.5	ENSP00000380794	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53473 AN: 151928 Hom.: 10636 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.419 AC: 521851 AN: 1246560 Hom.: 111969 AF XY: 0.423 AC XY: 259781 AN XY: 614020

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.352 AC: 53486 AN: 152046 Hom.: 10648 Cov.: 32 AF XY: 0.357 AC XY: 26536 AN XY: 74302

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.368

Alfa AF: 0.421 Hom.: 6671

Bravo AF: 0.339

Asia WGS AF: 0.406 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.51

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: rs2280934; hg19: chr8-23106665; COSMIC: COSV57533803;