chr17-48073499-T-G

Variant names:

• chr17-48073499-T-G
• rs7224014
• NM_001127228.2:c.413+1507A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127228.2(CBX1):​c.413+1507A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,024 control chromosomes in the GnomAD database, including 6,363 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 (6363 hom., cov: 31)
• Consequence: CBX1 NM_001127228.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 6 publications found

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]

CBX1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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 rank	MANE	Protein	UniProt
CBX1	NM_001127228.2	c.413+1507A>C		intron_variant	Intron 4 of 4	ENST00000225603.9	NP_001120700.1
CBX1	NM_006807.5	c.413+1507A>C		intron_variant	Intron 4 of 4		NP_006798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9	c.413+1507A>C		intron_variant	Intron 4 of 4	1	NM_001127228.2	ENSP00000225603.4
CBX1	ENST00000393408.7	c.413+1507A>C		intron_variant	Intron 4 of 4	1		ENSP00000377060.3
CBX1	ENST00000581003.5	c.413+1507A>C		intron_variant	Intron 5 of 5	3		ENSP00000462242.1
CBX1	ENST00000402583.5	c.425+1507A>C		intron_variant	Intron 4 of 4	4		ENSP00000385413.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41373 AN: 151906 Hom.: 6355 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.272 AC: 41406 AN: 152024 Hom.: 6363 Cov.: 31 AF XY: 0.267 AC XY: 19850 AN XY: 74300

African (AFR) AF: 0.425 AC: 17610 AN: 41410

American (AMR) AF: 0.184 AC: 2816 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3466

East Asian (EAS) AF: 0.190 AC: 985 AN: 5174

South Asian (SAS) AF: 0.207 AC: 997 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2532 AN: 10574

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14834 AN: 68000

Other (OTH) AF: 0.250 AC: 526 AN: 2108

Alfa AF: 0.263 Hom.: 643

Bravo AF: 0.276

Asia WGS AF: 0.192 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7224014; hg19: chr17-46150861;