rs11597439

Positions:

• chr10-102425196-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024040.3(CUEDC2):​c.-8G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,609,758 control chromosomes in the GnomAD database, including 92,013 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 0.29 (7060 hom., cov: 32)
  • Exomes 𝑓: 0.34 (84953 hom.)
• Consequence: CUEDC2 NM_024040.3 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

CUEDC2 (HGNC:28352): (CUE domain containing 2) Predicted to enable ubiquitin binding activity. Acts upstream of or within negative regulation of cytokine production involved in inflammatory response and negative regulation of macrophage cytokine production. Located in cytosol; nuclear membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CUEDC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUEDC2	NM_024040.3	c.-8G>C		splice_region_variant	2/9	ENST00000369937.5	NP_076945.2
CUEDC2	NM_024040.3	c.-8G>C		5_prime_UTR_variant	2/9	ENST00000369937.5	NP_076945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUEDC2	ENST00000369937.5	c.-8G>C		splice_region_variant	2/9	1	NM_024040.3	ENSP00000358953.4
CUEDC2	ENST00000369937.5	c.-8G>C		5_prime_UTR_variant	2/9	1	NM_024040.3	ENSP00000358953.4
CUEDC2	ENST00000477994.1	n.62G>C		splice_region_variant, non_coding_transcript_exon_variant	2/5	2
CUEDC2	ENST00000486762.6	n.44-404G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44275 AN: 151952 Hom.: 7063 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.330

GnomAD3 exomes AF: 0.342 AC: 85049 AN: 248508 Hom.: 15439 AF XY: 0.350 AC XY: 47241 AN XY: 134896

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.449

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.336 AC: 489767 AN: 1457688 Hom.: 84953 Cov.: 32 AF XY: 0.340 AC XY: 246816 AN XY: 725372

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.452

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.291 AC: 44272 AN: 152070 Hom.: 7060 Cov.: 32 AF XY: 0.295 AC XY: 21908 AN XY: 74326

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.326

Alfa AF: 0.275 Hom.: 1399

Bravo AF: 0.286

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11597439; hg19: chr10-104184953; COSMIC: COSV56523173; COSMIC: COSV56523173;