rs2240122

Variant names:

• chr17-48075197-C-A
• rs2240122
• NM_001127228.2:c.319-97G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.76).
• 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 rank	MANE	Protein	UniProt
CBX1	NM_001127228.2	c.319-97G>T		intron_variant	Intron 3 of 4	ENST00000225603.9	NP_001120700.1
CBX1	NM_006807.5	c.319-97G>T		intron_variant	Intron 3 of 4		NP_006798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX1	ENST00000225603.9	c.319-97G>T		intron_variant	Intron 3 of 4	1	NM_001127228.2	ENSP00000225603.4

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

African (AFR) AF: 0.243 AC: 2998 AN: 12348

American (AMR) AF: 0.0802 AC: 1643 AN: 20498

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 1621 AN: 13834

East Asian (EAS) AF: 0.0205 AC: 586 AN: 28558

South Asian (SAS) AF: 0.105 AC: 4738 AN: 45280

European-Finnish (FIN) AF: 0.120 AC: 4395 AN: 36594

Middle Eastern (MID) AF: 0.150 AC: 502 AN: 3350

European-Non Finnish (NFE) AF: 0.102 AC: 30918 AN: 302420

Other (OTH) AF: 0.105 AC: 2667 AN: 25330

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

African (AFR) AF: 0.296 AC: 11902 AN: 40238

American (AMR) AF: 0.111 AC: 1616 AN: 14516

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 446 AN: 3400

East Asian (EAS) AF: 0.00121 AC: 6 AN: 4978

South Asian (SAS) AF: 0.0985 AC: 452 AN: 4590

European-Finnish (FIN) AF: 0.122 AC: 1131 AN: 9274

Middle Eastern (MID) AF: 0.142 AC: 41 AN: 288

European-Non Finnish (NFE) AF: 0.116 AC: 7624 AN: 65866

Other (OTH) AF: 0.159 AC: 317 AN: 1998

Alfa AF: 0.200 Hom.: 1742

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
PhyloP100		0.13
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: rs2240122; hg19: chr17-46152559;