rs1920045

Positions:

• chr12-54276614-C-T

Variant summary

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

The NM_012117.3(CBX5):​c.-43+3394G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,038 control chromosomes in the GnomAD database, including 22,518 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 0.52 (22517 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: CBX5 NM_012117.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609

Genes affected

CBX5 (HGNC:1555): (chromobox 5) This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family. The protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The encoded product is involved in the formation of functional kinetochore through interaction with essential kinetochore proteins. The gene has a pseudogene located on chromosome 3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SCAT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX5	NM_012117.3	c.-43+3394G>A		intron_variant		ENST00000209875.9	NP_036249.1
SCAT2	NR_157844.1	n.324-2038C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX5	ENST00000209875.9	c.-43+3394G>A		intron_variant		1	NM_012117.3	ENSP00000209875.4
SCAT2	ENST00000547177.1	n.324-2038C>T		intron_variant		3
CBX5	ENST00000618078.1	n.127-2273G>A		intron_variant		2
ENSG00000258344	ENST00000553061.1	n.-17C>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78774 AN: 151916 Hom.: 22469 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.519 AC: 78881 AN: 152034 Hom.: 22517 Cov.: 32 AF XY: 0.523 AC XY: 38835 AN XY: 74296

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.455

Alfa AF: 0.409 Hom.: 17650

Bravo AF: 0.528

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.63

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: rs1920045; hg19: chr12-54670398;