chr8-23249152-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152272.5(CHMP7):​c.300-58A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,249,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CHMP7 NM_152272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>T		intron	N/A	NP_689485.1	Q8WUX9-1
	CHMP7	NM_001363183.2		c.300-58A>T		intron	N/A	NP_001350112.1
	CHMP7	NM_001317899.2		c.-31-58A>T		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>T		intron	N/A	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000313219.8	TSL:1	c.300-58A>T		intron	N/A	ENSP00000324491.7	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.300-58A>T		intron	N/A	ENSP00000550334.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1249072 Hom.: 0 AF XY: 0.00000163 AC XY: 1 AN XY: 615264

African (AFR) AF: 0.00 AC: 0 AN: 27722

American (AMR) AF: 0.00 AC: 0 AN: 25626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18914

East Asian (EAS) AF: 0.00 AC: 0 AN: 36436

South Asian (SAS) AF: 0.00 AC: 0 AN: 62708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3490

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 973674

Other (OTH) AF: 0.00 AC: 0 AN: 51644

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.92
DANN	Benign	0.75
PhyloP100		-0.11

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

Other links and lift over

dbSNP: rs2280934; hg19: chr8-23106665;