chr8-23252990-C-T

Position:

• chr8-23252990-C-T

Variant summary

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

The ENST00000397677.6(CHMP7):​c.472-2257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,096 control chromosomes in the GnomAD database, including 9,522 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 (9522 hom., cov: 32)
• Consequence: CHMP7 ENST00000397677.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.472-2257C>T		intron_variant		ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.472-2257C>T		intron_variant		1	NM_152272.5	ENSP00000380794	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51101 AN: 151976 Hom.: 9507 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.336 AC: 51138 AN: 152096 Hom.: 9522 Cov.: 32 AF XY: 0.341 AC XY: 25324 AN XY: 74354

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.347

Alfa AF: 0.384 Hom.: 7000

Bravo AF: 0.325

Asia WGS AF: 0.419 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.56

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: rs11135712; hg19: chr8-23110503;