rs4934719

Variant names:

• chr10-35087841-T-C
• rs4934719
• NM_003591.4:c.-23+2338A>G

Variant summary

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

The NM_003591.4(CUL2):​c.-23+2338A>G 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 151,814 control chromosomes in the GnomAD database, including 7,047 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 (7047 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• 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 (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	NM_003591.4	c.-23+2338A>G		intron_variant	Intron 1 of 20	ENST00000374749.8	NP_003582.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000374749.8	c.-23+2338A>G		intron_variant	Intron 1 of 20	1	NM_003591.4	ENSP00000363881.3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44443 AN: 151694 Hom.: 7036 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.293 AC: 44488 AN: 151814 Hom.: 7047 Cov.: 32 AF XY: 0.296 AC XY: 21929 AN XY: 74158

African (AFR) AF: 0.162 AC: 6707 AN: 41408

American (AMR) AF: 0.300 AC: 4562 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1387 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1525 AN: 5134

South Asian (SAS) AF: 0.349 AC: 1675 AN: 4802

European-Finnish (FIN) AF: 0.390 AC: 4105 AN: 10526

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

European-Non Finnish (NFE) AF: 0.346 AC: 23520 AN: 67950

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.325 Hom.: 4574

Bravo AF: 0.279

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4934719; hg19: chr10-35376769;