rs2280934

Variant names:

• chr8-23249152-A-G
• rs2280934
• NM_152272.5:c.300-58A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-23249152-A-G
• chr8-23249152-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP7	NM_152272.5	MANE Select	c.300-58A>G		intron	N/A	NP_689485.1	Q8WUX9-1
	CHMP7	NM_001363183.2		c.300-58A>G		intron	N/A	NP_001350112.1
	CHMP7	NM_001317899.2		c.-31-58A>G		intron	N/A	NP_001304828.1	B3KRZ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP7	ENST00000397677.6	TSL:1 MANE Select	c.300-58A>G		intron	N/A	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000313219.8	TSL:1	c.300-58A>G		intron	N/A	ENSP00000324491.7	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.300-58A>G		intron	N/A	ENSP00000550334.1

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

African (AFR) AF: 0.139 AC: 3845 AN: 27718

American (AMR) AF: 0.457 AC: 11696 AN: 25592

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 8843 AN: 18874

East Asian (EAS) AF: 0.405 AC: 14750 AN: 36392

South Asian (SAS) AF: 0.530 AC: 33173 AN: 62570

European-Finnish (FIN) AF: 0.436 AC: 21278 AN: 48812

Middle Eastern (MID) AF: 0.474 AC: 1655 AN: 3488

European-Non Finnish (NFE) AF: 0.417 AC: 405617 AN: 971586

Other (OTH) AF: 0.407 AC: 20994 AN: 51528

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

African (AFR) AF: 0.149 AC: 6192 AN: 41490

American (AMR) AF: 0.440 AC: 6725 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1663 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1724 AN: 5164

South Asian (SAS) AF: 0.518 AC: 2498 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4549 AN: 10542

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28861 AN: 67970

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.418 Hom.: 7365

Bravo AF: 0.339

Asia WGS AF: 0.406 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2280934;

hg19: chr8-23106665;

COSMIC: COSV57533803;