8-23244107-T-C

Variant names:

• chr8-23244107-T-C
• rs7463256
• NM_152272.5:c.-441+263T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152272.5(CHMP7):​c.-441+263T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,910 control chromosomes in the GnomAD database, including 9,547 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 0.33 (9547 hom., cov: 31)
• Consequence: CHMP7 NM_152272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 21 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 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.-441+263T>C		intron	N/A	NP_689485.1	Q8WUX9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP7	ENST00000397677.6	TSL:1 MANE Select	c.-441+263T>C		intron	N/A	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.-441+295T>C		intron	N/A	ENSP00000550334.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50411 AN: 151792 Hom.: 9536 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.332 AC: 50424 AN: 151910 Hom.: 9547 Cov.: 31 AF XY: 0.337 AC XY: 25030 AN XY: 74212

African (AFR) AF: 0.136 AC: 5624 AN: 41458

American (AMR) AF: 0.426 AC: 6496 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1581 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1726 AN: 5170

South Asian (SAS) AF: 0.488 AC: 2348 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4219 AN: 10488

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27244 AN: 67948

Other (OTH) AF: 0.343 AC: 722 AN: 2106

Alfa AF: 0.384 Hom.: 13979

Bravo AF: 0.321

Asia WGS AF: 0.393 AC: 1364 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.6
DANN	Benign	0.96
PhyloP100		0.31
PromoterAI		-0.0042	Neutral
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

Other links and lift over

dbSNP: rs7463256; hg19: chr8-23101620;