rs6847

Positions:

• chr17-48070445-T-A

Variant summary

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

The NM_001127228.2(CBX1):​c.*990A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,502 control chromosomes in the GnomAD database, including 6,385 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 0.27 (6374 hom., cov: 32)
  • Exomes 𝑓: 0.21 (11 hom.)
• Consequence: CBX1 NM_001127228.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBX1	NM_001127228.2	c.*990A>T		3_prime_UTR_variant	5/5	ENST00000225603.9	NP_001120700.1
CBX1	NM_006807.5	c.*990A>T		3_prime_UTR_variant	5/5		NP_006798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9	c.*990A>T		3_prime_UTR_variant	5/5	1	NM_001127228.2	ENSP00000225603	P1
CBX1	ENST00000393408.7	c.*990A>T		3_prime_UTR_variant	5/5	1		ENSP00000377060	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41411 AN: 151944 Hom.: 6366 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.207 AC: 91 AN: 440 Hom.: 11 Cov.: 0 AF XY: 0.225 AC XY: 59 AN XY: 262

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.273 AC: 41444 AN: 152062 Hom.: 6374 Cov.: 32 AF XY: 0.267 AC XY: 19884 AN XY: 74352

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.250

Alfa AF: 0.247 Hom.: 676

Bravo AF: 0.276

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.66

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: rs6847; hg19: chr17-46147807; COSMIC: COSV56681827; COSMIC: COSV56681827;