chr17-79834118-T-TGCCGCC

Variant names:

• chr17-79834118-T-TGCCGCC
• rs754126884
• NM_003655.3:c.1518_1523dupGGCGGC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_003655.3(CBX4):​c.1518_1523dupGGCGGC​(p.Ala507_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 0.091 in 1,602,562 control chromosomes in the GnomAD database, including 7,718 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (679 hom., cov: 31)
  • Exomes 𝑓: 0.091 (7039 hom.)
• Consequence: CBX4 NM_003655.3 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.910
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003655.3
• BP6: Variant 17-79834118-T-TGCCGCC is Benign according to our data. Variant chr17-79834118-T-TGCCGCC is described in ClinVar as Benign. ClinVar VariationId is 769436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX4	NM_003655.3	c.1518_1523dupGGCGGC	p.Ala507_Ala508dup	disruptive_inframe_insertion	Exon 5 of 5	ENST00000269397.9	NP_003646.2
CBX4	XM_011525399.3	c.1320_1325dupGGCGGC	p.Ala441_Ala442dup	disruptive_inframe_insertion	Exon 3 of 3		XP_011523701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX4	ENST00000269397.9	c.1518_1523dupGGCGGC	p.Ala507_Ala508dup	disruptive_inframe_insertion	Exon 5 of 5	1	NM_003655.3	ENSP00000269397.4

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13829 AN: 151958 Hom.: 676 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0767

GnomAD2 exomes AF: 0.0823 AC: 19001 AN: 230972 AF XY: 0.0898

Gnomad AFR exome AF: 0.0934

Gnomad AMR exome AF: 0.0503

Gnomad ASJ exome AF: 0.0838

Gnomad EAS exome AF: 0.00174

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0827

Gnomad OTH exome AF: 0.0757

GnomAD4 exome AF: 0.0910 AC: 132046 AN: 1450488 Hom.: 7039 Cov.: 32 AF XY: 0.0948 AC XY: 68325 AN XY: 720716

African (AFR) AF: 0.107 AC: 3494 AN: 32720

American (AMR) AF: 0.0535 AC: 2337 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.0912 AC: 2353 AN: 25812

East Asian (EAS) AF: 0.00166 AC: 65 AN: 39258

South Asian (SAS) AF: 0.195 AC: 16580 AN: 85130

European-Finnish (FIN) AF: 0.0530 AC: 2734 AN: 51580

Middle Eastern (MID) AF: 0.117 AC: 669 AN: 5710

European-Non Finnish (NFE) AF: 0.0891 AC: 98603 AN: 1106878

Other (OTH) AF: 0.0872 AC: 5211 AN: 59752

GnomAD4 genome AF: 0.0910 AC: 13841 AN: 152074 Hom.: 679 Cov.: 31 AF XY: 0.0910 AC XY: 6765 AN XY: 74360

African (AFR) AF: 0.105 AC: 4371 AN: 41488

American (AMR) AF: 0.0753 AC: 1151 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3470

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5166

South Asian (SAS) AF: 0.191 AC: 921 AN: 4816

European-Finnish (FIN) AF: 0.0541 AC: 574 AN: 10608

Middle Eastern (MID) AF: 0.100 AC: 29 AN: 290

European-Non Finnish (NFE) AF: 0.0914 AC: 6211 AN: 67922

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0485 Hom.: 69

Asia WGS AF: 0.0710 AC: 246 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91
Mutation Taster		=85/15	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs754126884; hg19: chr17-77807917; COSMIC: COSV53964435; COSMIC: COSV53964435;