8-23244107-T-C

Position:

• chr8-23244107-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.-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

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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHMP7	NM_152272.5	c.-441+263T>C		intron_variant		ENST00000397677.6
CHMP7	XM_047422416.1	c.-441+263T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHMP7	ENST00000397677.6	c.-441+263T>C		intron_variant		1	NM_152272.5	P1

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.343

Alfa AF: 0.393 Hom.: 11107

Bravo AF: 0.321

Asia WGS AF: 0.393 AC: 1364 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.6
DANN	Benign	0.96

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: rs7463256; hg19: chr8-23101620;