rs12240347

Variant names:

• chr10-35070547-A-G
• rs12240347
• NM_003591.4:c.119+652T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003591.4(CUL2):​c.119+652T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,034 control chromosomes in the GnomAD database, including 10,109 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 0.36 (10109 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 12 publications found

Genes affected

CUL2 (HGNC:2552): (cullin 2) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within protein catabolic process. Located in nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	NM_003591.4	MANE Select	c.119+652T>C		intron	N/A	NP_003582.2
	CUL2	NM_001198778.2		c.176+652T>C		intron	N/A	NP_001185707.1
	CUL2	NM_001198779.1		c.158+652T>C		intron	N/A	NP_001185708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL2	ENST00000374749.8	TSL:1 MANE Select	c.119+652T>C		intron	N/A	ENSP00000363881.3
	CUL2	ENST00000374751.7	TSL:1	c.119+652T>C		intron	N/A	ENSP00000363883.3
	CUL2	ENST00000421317.5	TSL:2	c.176+652T>C		intron	N/A	ENSP00000414095.2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55179 AN: 151916 Hom.: 10081 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.364 AC: 55266 AN: 152034 Hom.: 10109 Cov.: 32 AF XY: 0.363 AC XY: 26995 AN XY: 74310

African (AFR) AF: 0.404 AC: 16770 AN: 41460

American (AMR) AF: 0.324 AC: 4945 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1640 AN: 5174

South Asian (SAS) AF: 0.350 AC: 1683 AN: 4814

European-Finnish (FIN) AF: 0.389 AC: 4113 AN: 10568

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23612 AN: 67970

Other (OTH) AF: 0.372 AC: 784 AN: 2106

Alfa AF: 0.353 Hom.: 24275

Bravo AF: 0.359

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12240347; hg19: chr10-35359475;