chr8-23246928-A-T

Variant names:

• chr8-23246928-A-T
• rs775727289
• NM_152272.5:c.233A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_152272.5(CHMP7):​c.233A>T​(p.Gln78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000447 in 1,564,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29328993).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.233A>T	p.Gln78Leu	missense	Exon 2 of 11	NP_689485.1	Q8WUX9-1
	CHMP7	NM_001363183.2		c.233A>T	p.Gln78Leu	missense	Exon 1 of 9	NP_001350112.1
	CHMP7	NM_001317899.2		c.-32+104A>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.233A>T	p.Gln78Leu	missense	Exon 2 of 11	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000313219.8	TSL:1	c.233A>T	p.Gln78Leu	missense	Exon 1 of 10	ENSP00000324491.7	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.233A>T	p.Gln78Leu	missense	Exon 2 of 11	ENSP00000550334.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1412360 Hom.: 0 Cov.: 36 AF XY: 0.00000143 AC XY: 1 AN XY: 698406

African (AFR) AF: 0.00 AC: 0 AN: 32538

American (AMR) AF: 0.0000269 AC: 1 AN: 37156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25268

East Asian (EAS) AF: 0.00 AC: 0 AN: 37266

South Asian (SAS) AF: 0.00 AC: 0 AN: 80648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088080

Other (OTH) AF: 0.0000171 AC: 1 AN: 58540

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.1
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.098
Sift	Benign	0.14	T
Sift4G	Uncertain	0.037	D
Polyphen		0.013	B
Vest4		0.31
MutPred		0.37		Loss of disorder (P = 0.0452)
MVP		0.68
MPC		0.61
ClinPred		0.88	D
GERP RS		5.2
PromoterAI		0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.75
Mutation Taster		=75/25	polymorphism

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: rs775727289; hg19: chr8-23104441;