rs3751954

chr17-79779686-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005189.3(CBX2):c.182+259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 531,454 control chromosomes in the GnomAD database, including 3,687 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 0.10 (994 hom., cov: 34)
  • Exomes 𝑓: 0.11 (2693 hom.)
• Consequence: CBX2 NM_005189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

CBX2 (HGNC:1552): (chromobox 2) This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBX2	NM_005189.3	c.182+259A>G		intron_variant		ENST00000310942.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBX2	ENST00000310942.9	c.182+259A>G		intron_variant		1	NM_005189.3	P1
CBX2	ENST00000269399.5	c.182+259A>G		intron_variant		1
CBX2	ENST00000571484.1	n.514A>G		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 152180 Hom.: 987 Cov.: 34

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.112 AC: 42554 AN: 379156 Hom.: 2693 Cov.: 0 AF XY: 0.111 AC XY: 22024 AN XY: 198336

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.0947

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.101 AC: 15377 AN: 152298 Hom.: 994 Cov.: 34 AF XY: 0.104 AC XY: 7723 AN XY: 74476

Gnomad4 AFR AF: 0.0484

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.0700

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.106

Alfa AF: 0.111 Hom.: 331

Bravo AF: 0.105

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.3
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs3751954; hg19: chr17-77753485;