17-48075197-C-T

Position:

• 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>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 635,592 control chromosomes in the GnomAD database, including 2,799 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 0.12 (1058 hom., cov: 30)
  • Exomes 𝑓: 0.11 (1741 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17150 AN: 145996 Hom.: 1057 Cov.: 30

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0932

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0984

GnomAD4 exome AF: 0.114 AC: 55831 AN: 489534 Hom.: 1741 AF XY: 0.113 AC XY: 29406 AN XY: 259110

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0726

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.118 AC: 17162 AN: 146058 Hom.: 1058 Cov.: 30 AF XY: 0.117 AC XY: 8328 AN XY: 70910

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.0932

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.101

Alfa AF: 0.00707 Hom.: 1455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.89

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; COSMIC: COSV56682770;