rs11593858

Variant names:

• chr10-35092445-G-A
• rs11593858
• ENST00000685421.1:c.167+8399C>T

Variant summary

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

The ENST00000685421.1(CUL2):​c.167+8399C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,076 control chromosomes in the GnomAD database, including 7,063 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 (7063 hom., cov: 33)
• Consequence: CUL2 ENST00000685421.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL2	XM_011519743.1	c.167+8399C>T		intron_variant	Intron 3 of 22		XP_011518045.1
CUL2	XM_011519744.1	c.167+8399C>T		intron_variant	Intron 2 of 21		XP_011518046.1
CUL2	XM_011519745.2	c.167+8399C>T		intron_variant	Intron 2 of 21		XP_011518047.1
CUL2	XM_047425852.1	c.167+8399C>T		intron_variant	Intron 3 of 22		XP_047281808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000685421.1	c.167+8399C>T		intron_variant	Intron 2 of 5			ENSP00000509605.1
CUL2	ENST00000686156.1	c.167+8399C>T		intron_variant	Intron 2 of 5			ENSP00000509166.1
CUL2	ENST00000688736.1	c.167+8399C>T		intron_variant	Intron 3 of 6			ENSP00000510643.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44523 AN: 151958 Hom.: 7051 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.293 AC: 44571 AN: 152076 Hom.: 7063 Cov.: 33 AF XY: 0.296 AC XY: 21974 AN XY: 74330

African (AFR) AF: 0.163 AC: 6778 AN: 41504

American (AMR) AF: 0.299 AC: 4562 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1525 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4117 AN: 10542

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23520 AN: 67968

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.325 Hom.: 4576

Bravo AF: 0.279

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.75
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs11593858; hg19: chr10-35381373;