chr8-23258812-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152272.5(CHMP7):​c.1041C>T​(p.Leu347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,611,206 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 22 hom. )

Consequence

CHMP7
NM_152272.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.971
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 8-23258812-C-T is Benign according to our data. Variant chr8-23258812-C-T is described in ClinVar as [Benign]. Clinvar id is 782034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.971 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1593/152134) while in subpopulation AFR AF= 0.0359 (1487/41468). AF 95% confidence interval is 0.0343. There are 28 homozygotes in gnomad4. There are 737 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1593 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHMP7NM_152272.5 linkuse as main transcriptc.1041C>T p.Leu347= synonymous_variant 8/11 ENST00000397677.6 NP_689485.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHMP7ENST00000397677.6 linkuse as main transcriptc.1041C>T p.Leu347= synonymous_variant 8/111 NM_152272.5 ENSP00000380794 P1Q8WUX9-1

Frequencies

GnomAD3 genomes
AF:
0.0105
AC:
1590
AN:
152016
Hom.:
28
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0359
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00531
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:
0.000132
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00270
AC:
676
AN:
250546
Hom.:
9
AF XY:
0.00183
AC XY:
248
AN XY:
135458
show subpopulations
Gnomad AFR exome
AF:
0.0362
Gnomad AMR exome
AF:
0.00203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.00119
AC:
1735
AN:
1459072
Hom.:
22
Cov.:
30
AF XY:
0.00101
AC XY:
733
AN XY:
725962
show subpopulations
Gnomad4 AFR exome
AF:
0.0392
Gnomad4 AMR exome
AF:
0.00224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000159
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
AF:
0.0105
AC:
1593
AN:
152134
Hom.:
28
Cov.:
31
AF XY:
0.00991
AC XY:
737
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0359
Gnomad4 AMR
AF:
0.00530
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00250
Hom.:
5
Bravo
AF:
0.0123
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000475

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
CADD
Benign
2.7
DANN
Benign
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35799523; hg19: chr8-23116325; API