rs11597439

Variant names:

• chr10-102425196-C-G
• rs11597439
• NM_024040.3:c.-8G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUEDC2	NM_024040.3	MANE Select	c.-8G>C		splice_region	Exon 2 of 9	NP_076945.2	Q9H467
	CUEDC2	NM_024040.3	MANE Select	c.-8G>C		5_prime_UTR	Exon 2 of 9	NP_076945.2	Q9H467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUEDC2	ENST00000369937.5	TSL:1 MANE Select	c.-8G>C		splice_region	Exon 2 of 9	ENSP00000358953.4	Q9H467
	CUEDC2	ENST00000369937.5	TSL:1 MANE Select	c.-8G>C		5_prime_UTR	Exon 2 of 9	ENSP00000358953.4	Q9H467
	CUEDC2	ENST00000888785.1		c.-8G>C		splice_region	Exon 2 of 9	ENSP00000558844.1

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

GnomAD2 exomes AF: 0.342 AC: 85049 AN: 248508 AF XY: 0.350

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 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

African (AFR) AF: 0.152 AC: 5072 AN: 33424

American (AMR) AF: 0.393 AC: 17548 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9005 AN: 26112

East Asian (EAS) AF: 0.210 AC: 8351 AN: 39674

South Asian (SAS) AF: 0.452 AC: 38924 AN: 86190

European-Finnish (FIN) AF: 0.340 AC: 18001 AN: 52910

Middle Eastern (MID) AF: 0.438 AC: 2522 AN: 5760

European-Non Finnish (NFE) AF: 0.334 AC: 370575 AN: 1108668

Other (OTH) AF: 0.328 AC: 19769 AN: 60270

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

African (AFR) AF: 0.158 AC: 6542 AN: 41494

American (AMR) AF: 0.356 AC: 5441 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1166 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5158

South Asian (SAS) AF: 0.442 AC: 2133 AN: 4822

European-Finnish (FIN) AF: 0.334 AC: 3534 AN: 10582

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23283 AN: 67946

Other (OTH) AF: 0.326 AC: 687 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

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