rs4934719

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.580
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
CUL2NM_003591.4 linkuse as main transcriptc.-23+2338A>G intron_variant ENST00000374749.8 NP_003582.2 Q13617-1A0A140VKB1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUL2ENST00000374749.8 linkuse as main transcriptc.-23+2338A>G intron_variant 1 NM_003591.4 ENSP00000363881.3 Q13617-1

Frequencies

GnomAD3 genomes
AF:
0.293
AC:
44443
AN:
151694
Hom.:
7036
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.162
Gnomad4 AMR
AF:
0.300
Gnomad4 ASJ
AF:
0.399
Gnomad4 EAS
AF:
0.297
Gnomad4 SAS
AF:
0.349
Gnomad4 FIN
AF:
0.390
Gnomad4 NFE
AF:
0.346
Gnomad4 OTH
AF:
0.324
Alfa
AF:
0.326
Hom.:
4111
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4934719; hg19: chr10-35376769; API