rs12768019

Positions:

• chr10-35100915-T-C

Variant summary

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

The ENST00000450742.5(ENSG00000230534):​n.294A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,980 control chromosomes in the GnomAD database, including 7,043 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 (7040 hom., cov: 31)
  • Exomes 𝑓: 0.40 (3 hom.)
• Consequence: ENST00000450742.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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/exons	MANE	UniProt
CUL2	XM_011519743.1	c.96A>G	p.Lys32=	synonymous_variant	3/23
CUL2	XM_011519744.1	c.96A>G	p.Lys32=	synonymous_variant	2/22
CUL2	XM_011519745.2	c.96A>G	p.Lys32=	synonymous_variant	2/22
CUL2	XM_047425852.1	c.96A>G	p.Lys32=	synonymous_variant	3/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000450742.5	n.294A>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44416 AN: 151794 Hom.: 7028 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.397 AC: 27 AN: 68 Hom.: 3 Cov.: 0 AF XY: 0.413 AC XY: 19 AN XY: 46

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.293 AC: 44464 AN: 151912 Hom.: 7040 Cov.: 31 AF XY: 0.295 AC XY: 21913 AN XY: 74218

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.323

Alfa AF: 0.326 Hom.: 4093

Bravo AF: 0.279

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12768019; hg19: chr10-35389843;