8-23246682-G-T

Variant names:

• chr8-23246682-G-T
• rs2294123
• NM_152272.5:c.-14G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152272.5(CHMP7):​c.-14G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,543,476 control chromosomes in the GnomAD database, including 121,796 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 (9559 hom., cov: 33)
  • Exomes 𝑓: 0.40 (112237 hom.)
• Consequence: CHMP7 NM_152272.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 23 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.-14G>T		5_prime_UTR_variant	Exon 2 of 11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.-14G>T		5_prime_UTR_variant	Exon 2 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50500 AN: 152012 Hom.: 9548 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.343

GnomAD2 exomes AF: 0.407 AC: 60923 AN: 149590 AF XY: 0.418

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.323

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.404

GnomAD4 exome AF: 0.398 AC: 553375 AN: 1391346 Hom.: 112237 Cov.: 35 AF XY: 0.403 AC XY: 276195 AN XY: 685830

African (AFR) AF: 0.126 AC: 3936 AN: 31350

American (AMR) AF: 0.440 AC: 15554 AN: 35382

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11087 AN: 25002

East Asian (EAS) AF: 0.404 AC: 14424 AN: 35670

South Asian (SAS) AF: 0.502 AC: 39603 AN: 78952

European-Finnish (FIN) AF: 0.412 AC: 19771 AN: 47984

Middle Eastern (MID) AF: 0.438 AC: 1797 AN: 4106

European-Non Finnish (NFE) AF: 0.395 AC: 424881 AN: 1075322

Other (OTH) AF: 0.388 AC: 22322 AN: 57578

GnomAD4 genome AF: 0.332 AC: 50513 AN: 152130 Hom.: 9559 Cov.: 33 AF XY: 0.337 AC XY: 25099 AN XY: 74382

African (AFR) AF: 0.135 AC: 5624 AN: 41534

American (AMR) AF: 0.425 AC: 6494 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1576 AN: 3466

East Asian (EAS) AF: 0.333 AC: 1718 AN: 5160

South Asian (SAS) AF: 0.487 AC: 2351 AN: 4824

European-Finnish (FIN) AF: 0.404 AC: 4275 AN: 10578

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27260 AN: 67962

Other (OTH) AF: 0.343 AC: 726 AN: 2116

Alfa AF: 0.386 Hom.: 25435

Bravo AF: 0.321

Asia WGS AF: 0.394 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		3.4
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	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: rs2294123; hg19: chr8-23104195; COSMIC: COSV57533033;