GeneBe

NM_003655.3:c.1521_1523dupGGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_003655.3(CBX4):​c.1521_1523dupGGC​(p.Ala508dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,954 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CBX4
NM_003655.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.910

Publications

3 publications found
Variant links:
Genes affected
CBX4 (HGNC:1554): (chromobox 4) Enables SUMO binding activity; SUMO ligase activity; and enzyme binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of PRC1 complex. Implicated in hepatocellular carcinoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_003655.3

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CBX4NM_003655.3 linkc.1521_1523dupGGC p.Ala508dup disruptive_inframe_insertion Exon 5 of 5 ENST00000269397.9 NP_003646.2 O00257-1A0A0S2Z5B2
CBX4XM_011525399.3 linkc.1323_1325dupGGC p.Ala442dup disruptive_inframe_insertion Exon 3 of 3 XP_011523701.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CBX4ENST00000269397.9 linkc.1521_1523dupGGC p.Ala508dup disruptive_inframe_insertion Exon 5 of 5 1 NM_003655.3 ENSP00000269397.4 O00257-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000433
AC:
1
AN:
230972
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000974
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1450954
Hom.:
0
Cov.:
32
AF XY:
0.00000277
AC XY:
2
AN XY:
720962
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
32744
American (AMR)
AF:
0.00
AC:
0
AN:
43700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25828
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39260
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85196
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51584
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
0.00000181
AC:
2
AN:
1107148
Other (OTH)
AF:
0.00
AC:
0
AN:
59780
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.258
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs754126884; hg19: chr17-77807917; API