rs877529

chr22-39146287-G-A

Variant summary

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

The NM_175709.5(CBX7):c.113+3502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,154 control chromosomes in the GnomAD database, including 13,832 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 0.42 (13832 hom., cov: 33)
• Consequence: CBX7 NM_175709.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

Genes affected

CBX7 (HGNC:1557): (chromobox 7) This gene encodes a protein that contains the CHROMO (CHRomatin Organization MOdifier) domain. The encoded protein is a component of the Polycomb repressive complex 1 (PRC1), and is thought to control the lifespan of several normal human cells. [provided by RefSeq, Oct 2016]

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 = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBX7	NM_175709.5	c.113+3502C>T		intron_variant		ENST00000216133.10
CBX7	NM_001346743.2	c.113+3502C>T		intron_variant
CBX7	NM_001346744.2	c.113+3502C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBX7	ENST00000216133.10	c.113+3502C>T		intron_variant		1	NM_175709.5	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64064 AN: 152036 Hom.: 13829 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.421 AC: 64078 AN: 152154 Hom.: 13832 Cov.: 33 AF XY: 0.415 AC XY: 30870 AN XY: 74378

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.402

Alfa AF: 0.427 Hom.: 18134

Bravo AF: 0.412

Asia WGS AF: 0.294 AC: 1024 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	0.93
Dann	Benign	0.48

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: rs877529; hg19: chr22-39542292;