rs2240122

Positions:

• chr17-48075197-C-A
• chr17-48075197-C-G
• chr17-48075197-C-T

Variant summary

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

The NM_001127228.2(CBX1):​c.319-97G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 634,236 control chromosomes in the GnomAD database, including 3,318 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 0.16 (2492 hom., cov: 30)
  • Exomes 𝑓: 0.10 (826 hom.)
• Consequence: CBX1 NM_001127228.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

Genes affected

CBX1 (HGNC:1551): (chromobox 1) 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 protein may play an important role in the epigenetic control of chromatin structure and gene expression. Several related pseudogenes are located on chromosomes 1, 3, and X. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBX1	NM_001127228.2	c.319-97G>T		intron_variant		ENST00000225603.9
CBX1	NM_006807.5	c.319-97G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBX1	ENST00000225603.9	c.319-97G>T		intron_variant		1	NM_001127228.2	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 23598 AN: 145962 Hom.: 2492 Cov.: 30

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0902

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.103 AC: 50068 AN: 488212 Hom.: 826 AF XY: 0.104 AC XY: 26784 AN XY: 258448

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.0802

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0205

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.162 AC: 23614 AN: 146024 Hom.: 2492 Cov.: 30 AF XY: 0.157 AC XY: 11151 AN XY: 70906

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00121

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.159

Alfa AF: 0.195 Hom.: 1455

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.8
DANN	Benign	0.87

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: rs2240122; hg19: chr17-46152559;