rs2294125

Positions:

• chr8-23260130-T-C

Variant summary

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

The NM_152272.5(CHMP7):​c.1121-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,607,370 control chromosomes in the GnomAD database, including 157,041 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 0.34 (11225 hom., cov: 32)
  • Exomes 𝑓: 0.44 (145816 hom.)
• Consequence: CHMP7 NM_152272.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP7	NM_152272.5	c.1121-14T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000397677.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP7	ENST00000397677.6	c.1121-14T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_152272.5	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52363 AN: 151978 Hom.: 11224 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.405 AC: 101508 AN: 250754 Hom.: 23242 AF XY: 0.415 AC XY: 56282 AN XY: 135570

Gnomad AFR exome AF: 0.0982

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.0282

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.437 AC: 636428 AN: 1455274 Hom.: 145816 Cov.: 30 AF XY: 0.440 AC XY: 319077 AN XY: 724364

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.0493

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.344 AC: 52363 AN: 152096 Hom.: 11225 Cov.: 32 AF XY: 0.344 AC XY: 25582 AN XY: 74318

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.360

Alfa AF: 0.444 Hom.: 15944

Bravo AF: 0.326

Asia WGS AF: 0.233 AC: 814 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	6.3
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2294125; hg19: chr8-23117643; COSMIC: COSV57532784; COSMIC: COSV57532784;