rs1265564

Positions:

• chr12-111270654-A-C

Variant summary

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

The ENST00000261726.11(CUX2):​c.301+6815A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,440 control chromosomes in the GnomAD database, including 9,219 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 0.30 (9219 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: CUX2 ENST00000261726.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

Genes affected

CUX2 (HGNC:19347): (cut like homeobox 2) This gene encodes a protein which contains three CUT domains and a homeodomain; both domains are DNA-binding motifs. A similar gene, whose gene product possesses different DNA-binding activities, is located on chromosome on chromosome 7. Two pseudogenes of this gene have been identified on chromosomes 10 and 4. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUX2	NM_015267.4	c.301+6815A>C		intron_variant		ENST00000261726.11	NP_056082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUX2	ENST00000261726.11	c.301+6815A>C		intron_variant		1	NM_015267.4	ENSP00000261726	P1
CUX2	ENST00000397643.3	c.481+6815A>C		intron_variant		1		ENSP00000380765
CUX2	ENST00000551604.2	n.562A>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45251 AN: 151310 Hom.: 9221 Cov.: 30

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.299 AC: 45237 AN: 151432 Hom.: 9219 Cov.: 30 AF XY: 0.289 AC XY: 21375 AN XY: 73908

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0865

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.322

Alfa AF: 0.421 Hom.: 5228

Bravo AF: 0.284

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.77
DANN	Benign	0.86

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: rs1265564; hg19: chr12-111708458;