12-111349088-T-C

Position:

• chr12-111349088-T-C

Variant summary

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

The NM_015267.4(CUX2):​c.*763T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,426 control chromosomes in the GnomAD database, including 18,227 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 0.43 (18218 hom., cov: 32)
  • Exomes 𝑓: 0.25 (9 hom.)
• Consequence: CUX2 NM_015267.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUX2	NM_015267.4	c.*763T>C		3_prime_UTR_variant	22/22	ENST00000261726.11	NP_056082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUX2	ENST00000261726.11	c.*763T>C		3_prime_UTR_variant	22/22	1	NM_015267.4	ENSP00000261726	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64575 AN: 151926 Hom.: 18174 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.246 AC: 94 AN: 382 Hom.: 9 Cov.: 0 AF XY: 0.239 AC XY: 52 AN XY: 218

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.425 AC: 64686 AN: 152044 Hom.: 18218 Cov.: 32 AF XY: 0.431 AC XY: 32028 AN XY: 74338

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.407

Alfa AF: 0.282 Hom.: 7417

Bravo AF: 0.457

Asia WGS AF: 0.690 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.21

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: rs7398833; hg19: chr12-111786892;